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Articles

Gut: A key player in the pathogenesis of type 2 diabetes?

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References

  • Adrian, T. E., Sagor, G. R., Savage, A. P., Bacarese-Hamilton, A. J., Hall, G. M. and Bloom, S. R. (1986). Peptide YY kinetics and effects on blood pressure and circulating pancreatic and gastrointestinal hormones and metabolites in man. J. Clin. Endocrinol Metab. 63(4):803–807.
  • Ahren, B. and Larsson, H.(1996). Peptide YY does not inhibit glucose-stimulated insulin secretion in humans. Eur. J. Endocrinol. 134(3):362–365.
  • Ahrén, B., Holst, J. J. and Efendic, S. (2000). Antidiabetogenic action of cholecystokinin-8 in type 2 diabetes. J. Clin. Endocrinol. Metab. 85(3):1043–1048.
  • Althage, M. C., Ford, E. L., Wang, S., Tso, P., Polonsky, K. S., and Wice, B. M. (2008). Targeted ablation of glucose-dependent insulinotropic polypeptide-producing cells in transgenic mice reduces obesity and insulin resistance induced by a high fat diet. J. Biol. Chem. 283(26):18365–18376.
  • Amini, P., Wadden, D., Cahill, F., Randell, E., Vasdev, S., Chen, X., Gulliver, W., Zhang, W., Zhang, H., Yi, Y. and Sun, G. (2012). Serum acylated ghrelin is negatively correlated with the insulin resistance in the CODING study. Plos One 7(9):e45657.
  • Anderwald, C., Brabant, G., Bernroider, E., Horn, R., Brehm, A., Waldhäusl, W. and Roden, M. (2003). Insulin-dependent modulation of plasma ghrelin and leptin concentrations is less pronounced in type 2 diabetic patients. Diabetes. 52(7):1792–1798.
  • Anini, Y. and Brubaker, P. L. (2003). Role of leptin in the regulation of glucagon-like peptide-1 secretion. Diabetes. 52(2):252–259.
  • Asmar, M., Tangaa, W., Madsbad, S., Hare, K., Astrup, A., Flint, A., Bülow, J. and Holst, J.J. (2010). On the role of glucose-dependent insulintropic polypeptide in postprandial metabolism in humans. Am. J. Physiol. Endocrinol. Metab. 298(3):E614–E621.
  • Backhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A., Semenkovich, C. F. and Gordon, J. I. (2004). The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. U S A. 101(44):15718–15723.
  • Bagger, J. I., Knop, F. K., Lund, A., Vestergaard, H., Holst, J. J. and Vilsboll, T. (2011). Impaired regulation of the incretin effect in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 96:737–745.
  • Bahrami, J., Longuet, C., Baggio, L. L., Li, K. and Drucker, D. J. (2010). Glucagon-like peptide-2 receptor modulates islet adaptation to metabolic stress in the ob/ob mouse. Gastroenterology, 96(3):737–745.
  • Baldassano, S. and Amato, A. (2014). GLP-2: What do we know? What are we going to discover?. Regul. Peptides 194–195:6–10.
  • Batterham, R. L., Cohen, M. A., Ellis, S. M., Le Roux, C. W., Withers, D. J., Frost, G. S. and Bloom, S. R. (2003). Inhibition of food intake in obese subjects by peptide YY 3–36. New Engl. J. Med., 349(10):941–948.
  • Bennet, H., Balhuizen, A., Medina, A., Dekker Nitert, M., Ottosson Laakso, E., Essén, S., Spégel, P., Storm, P., Krus, U., Wierup, N. and Fex, M. (2015). Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes. Peptides. 71:113–120.
  • Boey, D., Lin, S., Karl, T., Baldock, P., Lee, N., Enriquez, R. and Herzog, H. (2006). Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity. Diabetologia. 49(6):1360–1370.
  • Breen, D. M., Rasmussen, B. A., Côté, C. D., Jackson, V. M. and Lam, T. K. (2013). Nutrient-sensing mechanisms in the gut as therapeutic targets for diabetes. Diabetes. 62(9):3005–3013.
  • Broglio, F., Arvat, E., Benso, A., Gottero, C., Muccioli, G., Papotti, M., van der Lely, A. J., Deghenghi, R. and Ghigo, E. (2001). Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J. Clin. Endocrinol. Metab. 86(10):5083–5086.
  • Broglio, F., Prodam, F., Riganti, F., Gottero, C., Destefanis, S., Granata, R., Muccioli, G., Abribat, T., van der Lely, A. J. and Ghigo, E. (2008). The continuous infusion of acylated ghrelin enhances growth hormone secretion and worsens glucose metabolism in humans. J. Endocrinol. Invest. 31(9):788–794.
  • Broussard, J. L., Kilkus, J. M., Delebecque, F., Abraham, V., Day, A., Whitmore, H. R. and Tasali, E. (2016). Elevated ghrelin predicts food intake during experimental sleep restriction. Obesity (Silver Spring). 24(1):132–138.
  • Bulotta, A., Farilla, L., Hui, H. and Perfetti, R. (2004). The role of GLP-1 in the regulation of islet cell mass. Cell Biochem. Biophys. 40(3):65–78.
  • Burcelin, R., Serino, M., Chabo, C., Blasco-Baque, V. and Amar, J. (2011). Gut microbiota and diabetes: From pathogenesis to therapeutic perspective. Acta Diabetol. 48:257–273.
  • Camilleri, M., Papathanasopoulos, A. and Odunsi, S. T. (2009). Actions and therapeutic pathways of ghrelin for gastrointestinal disorders. Nat. Rev. Gastroenterol. Hepatol. 6(6):343–352.
  • Cani, P. D., Geurts, L., Matamoros, S., Plovier, H. and Duparc, T. (2014). Glucose metabolism: Focus on gut microbiota, the endocannabinoid system and beyond. Diab. Metab. 40(4):246–257.
  • Chia, C. W., Carlson, O. D., Kim, W., Shin, Y. K., Charles, C. P., Kim, H. S., Melvin, D. L. and Egan, J. M. (2009). Exogenous glucose-dependent insulinotropic polypeptide worsens post prandial hyperglycemia in type 2 diabetes. Diabetes. 58(6):1342–1349.
  • Christensen, M., Calanna, S., Sparre-Ulrich, A. H., Kristensen, P. L., Rosenkilde, M. M., Faber, J., Purrello, F., Van Hall, G., Holst, J. J., Vilsbøll, T., Knop, F. K. (2015). Glucose-dependent insulinotropic polypeptide augments glucagon responses to hypoglycemia in type 1 diabetes. Diabetes. 64(1):72–78.
  • Christensen, S. E., Hansen, A. P., Weeke, J. and Lundbaek, K. (1978). 24-hour studies of the effects of somatostatin on the levels of plasma growth hormone, glucagon, and glucose in normal subjects and juvenile diabetics. Diabetes. 27(3):300–306.
  • Cox, H. M., Tough, I. R., Woolston, A.-M., Zhang, L., Nguyen, A. D., Sainsbury, A. and Herzog, H. (2010). Peptide YY is critical for acylethanolamine receptor Gpr119-induced activation of gastrointestinal mucosal responses. Cell Metabolism. 11(6):532–542.
  • Crockett, S. E., Mazzaferri, E. L. and Cataland, S. (1976).Gastric inhibitory polypeptide (GIP) in maturity-onset diabetes mellitus. Diabetes. 25(10):931–935.
  • Cummings, D. E., Overduin, J., Foster-Schubert, K. E. and Carlson, M. J. (2007). Role of the bypassed proximal intestine in the anti-diabetic effects of bariatric surgery. Surg. Obesity Relat Diseases. 3(2):109–115.
  • Cummings, D. E., Purnell, J. Q., Frayo, R. S., Schmidova, K., Wisse, B. E. and Weigle, D. S. (2001). A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes. 50(8):1714–1749.
  • D'Alessio, D. A. and Ensinck, J. W. (1990). Fasting and postprandial concentrations of somatostatin-28 and somatostatin-14 in type II diabetes in men. Diabetes. 39(10):1198–1202.
  • Dash, S., Xiao, C., Morgantini, C., Connelly, P. W., Patterson, B. W. and Lewis, G. F. (2014). Glucagon-like peptide-2 regulates release of chylomicrons from the intestine. Gastroenterology. 147(6):1275–1284.e4.
  • De Heer, J., Pedersen, J., Orskov, C. and Holst, J. J. (2007). The alpha cell expresses glucagon-like peptide-2 receptors and glucagon-like peptide-2 stimulates glucagon secretion from the rat pancreas. Diabetologia. 50(10):2135–2142.
  • De Jonghe, B. C., Hajnal, A. and Covasa, M. (2005). Increased oral and decreased intestinal sensitivity to sucrose in obese, prediabetic CCK-A receptor-deficient OLETF rats. Am. J. Physiol. Regul. Integr. Comparat. Physiol. 288(1):R292–R300.
  • De Leon, D. D., Deng, S., Madani, R., Ahima, R. S., Drucker, D. J. and Stoffers, D. A. (2003). Role of endogenous glucagon-like peptide-1 in islet regeneration after partial pancreatectomy. Diabetes. 52(2):365–371.
  • De Luis, D., Domingo, M., Romero, A., Gonzalez Sagrado, M., Pacheco, D., Primo, D. and Conde, R. (2012). Effects of duodenal-jejunal exclusion on beta cell function and hormonal regulation in Goto-Kakizaki rats. Am. J. Surg., 204(2):242–247.
  • Dirksen, C., Hansen, D. L., Madsbad, S., Hvolris, L. E., Naver, L. S., Holst, J. J. and Worm, D. (2010). Postprandial diabetic glucose tolerance is normalized by gastric bypass feeding as opposed to gastric feeding and is associated with exaggerated GLP-1 secretion: A case report. Diabetes Care. 33:375–377.
  • Dupre, J., Curtis, J.D., Unger, R.H., Waddell, R. W. and Beck, J. C. (1969). Effects of secretin, pancreozymin, or gastrin on the response of the endocrine pancreas to administration of glucose or arginine in man. Clin. Invest. 48(4):745–757.
  • Edholm, T., Degerblad, M., Grybäck, P., Hilsted, L., Holst, J. J., Jacobsson, H., Efendic, S., Schmidt, P. T. and Hellström, P. M. (2010). Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis. Neurogastroenterol Motil. 22(11):1191–1200.
  • Egshatyan, L., Kashtanova, D., Popenko, A., Tkacheva, O., Tyakht, A., Alexeev, D., Karamnova, N., Kostryukova, E., Babenko, V., Vakhitova, M. and Boytsov, S. (2016). Gut microbiota and diet in patients with different glucose tolerance. Endocr. Connect. 5(1):1–9.
  • Eickhoff, H., Louro, T. M., Matafome, P. N., Vasconcelos, F., Seiça, R. M., Castro, E. and Sousa, F. (2015). Amelioration of glycemic control by sleeve gastrectomy and gastric bypass in a lean animal model of type 2 diabetes: Restoration of gut hormone profile. Obes. Surg. 25(1):7–18.
  • English, P. J., Ashcroft, A., Patterson, M., Dovey, T. M., Halford, J. C., Harrison, J., Eccleston, D., Bloom, S. R., Ghatei, M. A. and Wilding, J. P. (2006).Fasting plasma peptide-YY concentrations are elevated but do not rise postprandially in type 2 diabetes. Diabetologia. 49(9):2219–2221.
  • Erdmann, J., Lippl, F., Wagenpfeil, S. and Schusdziarra, V. (2005). Differential association of basal and postprandial plasma ghrelin with leptin, insulin, and type 2 diabetes. Diabetes. 54(5):1371–1378.
  • Faerch, K., Torekov, S. S., Vistisen, D., Johansen, N. B., Witte, D. R., Jonsson, A., Pedersen, O., Hansen, T., Lauritzen, T., Sandbæk, A., Holst, J. J., Jørgensen, M. E. (2015).GLP-1 response to oral glucose is reduced in prediabetes, screen-detected type 2 diabetes, and obesity and influenced by sex: The ADDITION-PRO study. Diabetes. 64(7):2513–2325.
  • Fang, S., Suh, J. M., Reilly, S. M., Yu, E., Osborn, O., Lackey, D., Yoshihara, E., Perino, A., Jacinto, S., Lukasheva, Y., Atkins, A. R., Khvat, A., Schnabl, B., Yu, R. T., Brenner, D. A., Coulter, S., Liddle, C., Schoonjans, K., Olefsky, J. M., Saltiel, A. R., Downes, M. and Evans, R. M. (2015). Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat. Med. 21(2):159–165.
  • Farilla, L., Hui, H., Bertolotto, C., Kang, E., Bulotta, A., Di Mario, U. and Perfetti, R. (2002). Glucagon-like peptide-1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats. Endocrinology. 143(11):4397–4408.
  • Fernández-García, J. C., Murri, M., Coin-Aragüez, L., Alcaide, J., El Bekay, R. and Tinahones, F. J. (2014).GLP-1 and peptide YY secretory response after fat load is impaired by insulin resistance, impaired fasting glucose and type 2 diabetes in morbidly obese subjects. Clin. Endocrinol (Oxf). 80(5):671–676.
  • Fidler, M. C., Sanchez, M., Raether, B., Weissman, N. J., Smith, S. R., Shanahan, W. R. and Anderson, C. M. (2011). BLOSSOM Clinical Trial Group.A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: The BLOSSOM trial. J. Clin. Endocrinol. Metab. 96(10):3067–3077.
  • Fleissner, C.K., Huebel, N., Abd El-Bary, M.M., Loh, G., Klaus, S., and Blaut, M. (2010). Absence of intestinal microbiota does not protect mice from dietinduced obesity. Br. J. Nutr. 104:919–929.
  • Flint, A., Raben, A., Astrup, A. and Holst, J. J. (1998). Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J. Clin. Invest. 101(3):515–520.
  • Forbes, S., Stafford, S., Coope, G., Heffron, H., Real, K., Newman, R. and Cox, H. (2015). Selective FFA2 agonism appears to act via intestinal PYY to reduce transit and food intake but does not improve glucose tolerance in mouse models. Diabetes. 64(11):3763–3771.
  • Fosgerau, K., Jessen, L., Lind Tolborg, J., Østerlund, T., Schæffer Larsen, K., Rolsted, K. and Skovlund Ryge Neerup, T. (2013). The novel GLP-1-gastrin dual agonist, ZP3022, increases β-cell mass and prevents diabetes in db/db mice. Diab. Obes. Metab. 15(1):62–71.
  • Foxx-Orenstein, A., Camilleri, M., Stephens, D. and Burton, D. (2003). Effect of a somatostatin analogue on gastric motor and sensory functions in healthy humans. Gut. 52(11):1555–1561.
  • Fukui, M., Shiraishi, E., Tanaka, M., Senmaru, T., Sakabe, K., Harusato, I., Hasegawa, G. and Nakamura, N. (2009). Plasma serotonin is a predictor for deterioration of urinary albumin excretion in men with type 2 diabetes mellitus. Metabolism. 58(8):1076–1079.
  • Fulurija, A., Lutz, T. A., Sladko, K., Osto, M., Wielinga, P. Y., Bachmann, M. F. and Saudan, P. (2008). Vaccination against GIP for the treatment of obesity. PLoS ONE. 3(9):e3163.
  • Gault, V. A., Porter, D., Irwin, N. and Flatt, P. R. (2011). Comparison of sub-chronic metabolic effects of stable forms of naturally occurring GIP(1–30) and GIP(1–42) in high fat fed mice. J. Endocrinology. 208(3):265–271.
  • Gauna, C., Delhanty, P. J. D., Hofland, L. J., Janssen, J. A. M. J. L., Broglio, F., Ross, R. J. M. and Van der Lely, A. J. (2005). Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J. Clin. Endocrinol. Metab. 90(2):1055–1060.
  • Gehlert, D. R. and Shaw, J. (2014). 5-Hydroxytryptamine 1A (5HT1A) receptors mediate increases in plasma glucose independent of corticosterone. Eur. J. Pharmacol. 745:91–7.
  • Geloneze, B., Lima, M. M., Pareja, J. C., Barreto, M. R. and Magro, D. O. (2013). Association of insulin resistance and GLP-2 secretion in obesity: A pilot study. Arq. Bras. Endocrinol. Metabol. 57(8):632–635.
  • Geurts, L., Lazarevic, V., Derrien, M., et al. (2011). Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: Impact on apelin regulation in adipose tissue. Front Microbiol. 2:1–17.
  • Glaser, B., Raveh, Y., Norynberg, C., Berry, E., Lavielle, R., Nathan, C. and Cerasi, E. (1992). Acute and chronic effects of dexfenfluramine on glucose and insulin response to intravenous glucose in diabetic and non-diabetic obese subjects. Diabetes Res. 19(4):165–176.
  • World Health Organization, Global report on diabetes. World Health Organization, Geneva, 2016.
  • Gniuli, D., Calcagno, A., Dalla Libera, L., Calvani, R., Leccesi, L., Caristo, M. E. and Mingrone, G. (2010). High-fat feeding stimulates endocrine, glucose-dependent insulinotropic polypeptide (GIP)-expressing cell hyperplasia in the duodenum of Wistar rats. Diabetologia. 53(10):2233–2240.
  • González-Ortiz, M., Martínez-Abundis, E., Mercado-Sesma, A. R. and Álvarez-Carrillo, R. (2015). Effect of pantoprazole on insulin secretion in drug-naïve patients with type 2 diabetes. Diabetes Res. Clin. Pract. 108(1):e11–e13.
  • Granata, R., Settanni, F., Biancone, L., Trovato, L., Nano, R., Bertuzzi, F. and Muccioli, G. (2007). Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: Involvement of 3′,5′-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inosit. Endocrinology. 148(2):512–529.
  • Grill, V., Gutniak, M., Roovete, A. and Efendić, S. (1984). A stimulating effect of glucose on somatostatin release is impaired in noninsulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 59(2):293–297.
  • Groop, P. H., Fyhrquist, F. and Groop, L. C. (1985).Effect of serial test meals on plasma immunoreactive GIP in non-insulin dependent diabetic patients and non-diabetic controls. Scand. J. Clin. Lab. Invest. 45(2):115–22.
  • Guo, Y., Ma, L., Enriori, P. J., Koska, J., Franks, P. W., Brookshire, T., Cowley, M. A., Salbe, A. D., Delparigi, A. and Tataranni, P. A. (2006). Physiological evidence for the involvement of peptide YY in the regulation of energy homeostasis in humans. Obesity (Silver Spring). 14(9):1562–1570.
  • Gutniak, M., Grill, V., Roovete, A. and Efendic, S. (1989). Impaired somatostatin response to orally administered glucose in type II diabetes entails both somatostatin-28 and -14 and is associated with deranged metabolic control. Acta Endocrinol. (Copenh) 121(3):322–326.
  • Gutzwiller, J. P, Drewe, J., Hildebrand, P., Rossi, L., Lauper, J. Z. and Beglinger, C. (1994). Effect of intravenous human gastrin-releasing peptide on food intake in humans. Gastroenterology. 106(5):1168–1173.
  • Gutzwiller, J. P., Drewe, J., Göke, B., Schmidt, H., Rohrer, B., Lareida, J. and Beglinger, C. (1999). Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am. J. Physiol. 276(5 Pt 2):R1541–R1544.
  • Guy-Grand, B., Apfelbaum, M., Crepaldi, G., Gries, A., Lefebvre, P. and Turner, P. (1989). International trial of long-term dexfenfluramine in obesity. Lancet. 2(8672):1142–1145.
  • Hauge-Evans, A. C., Bowe, J., Franklin, Z. J., Hassan, Z. and Jones, P. M. (2015). Inhibitory effect of somatostatin on insulin secretion is not mediated via the CNS. J. Endocrinology. 225(1):19–26.
  • Hauge-Evans, A. C., King, A. J., Carmignac, D., Richardson, C. C., Robinson, I. C. A. F., Low, M. J. and Jones, P. M. (2009). Somatostatin secreted by islet delta-cells fulfills multiple roles as a paracrine regulator of islet function. Diabetes. 58(2) 403–411.
  • He, C., Shan, Y. and Song, W.(2015). Targeting gut microbiota as a possible therapy for diabetes. Nutr. Res. 35(5):361–367.
  • Herzog, H. (2003). Neuropeptide Y and energy homeostasis: Insights from Y receptor knockout models. Eur. J. Pharmacology. 480(1–3):21–29.
  • Hildebrandt, M. A, Hoffmann, C., Sherrill-Mix, S. A, et al. (2009). High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 137:1716–1724.e1–2.
  • Hinke, S. A., Gelling, R. W., Pederson, R. A., Manhart, S., Nian, C., Demuth, H.-U. and McIntosh, C. H. S. (2002). Dipeptidyl peptidase IV-resistant [D-Ala2] glucose-dependent insulinotropic polypeptide (GIP) improves glucose tolerance in normal and obese diabetic rats. Diabetes. 51(3):652–661.
  • Hojberg, P. V. et al. (2009). Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia. 52:199–207.
  • Holst, J. J., Jensen, S. L., Knuhtsen, S. and Nielsen, O. V (1983). Autonomic nervous control of pancreatic somatostatin secretion. Am. J. Physiol. 245:E542–E548.
  • Iida, A., Seino, Y., Fukami, A., Maekawa, R., Yabe, D., Shimizu, S. and Hayashi, Y. (2016). Endogenous GIP ameliorates impairment of insulin secretion in proglucagon-deficient mice under moderate beta cell damage induced by streptozotocin. Diabetologia. 59(7):1533–1541.
  • Inci, F., Atmaca, M., Ozturk, M., Yildiz, S., Koceroglu, R., Sekeroglu, R., Ipekci, S.H. and Kebapcilar, L. (2014). Pantoprazole may improve beta cell function and diabetes mellitus. J. Endocrinol Invest. 37(5):449–454.
  • Iordanidou, M., Tavridou, A., Petridis, I., Arvanitidis, K.I., Christakidis, D., Vargemezis, V. and Manolopoulos, V. G. (2010). The serotonin transporter promoter polymorphism (5-HTTLPR) is associated with type 2 diabetes. Clin. Chim. Acta. 411(3–4):167–171.
  • Irwin, N. and Flatt, P. R. (2009). Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications. Diabetologia. 52(9):1724–1731.
  • Irwin, N., Hunter, K., Montgomery, I. A. and Flatt, P. R. (2013a). Comparison of independent and combined metabolic effects of chronic treatment with (pGlu-Gln)-CCK-8 and long-acting GLP-1 and GIP mimetics in high fat-fed mice. Diabetes, Obesity Metabolism. 15(7):650–659.
  • Irwin, N., Montgomery, I. A., Moffett, R. C. and Flatt, P. R. (2013). Chemical cholecystokinin receptor activation protects against obesity-diabetes in high fat fed mice and has sustainable beneficial effects in genetic ob/ob mice. Biochem. Pharmacology. 85(1):81–91.
  • Itoh, M., Hirooka, Y. and Nihei, N. (1983). Response of plasma somatostatin-like immunoreactivity (SLI) to a 75 g oral glucose tolerance test in normal subjects and patients with impaired glucose tolerance. Acta. Endocrinol. (Copenh). 104(4):468–474.
  • Jacoby, J. H. and Bryce, G. F. (1978). The acute pharmacologic effects of serotonin on the release of insulin and glucagon in the intact rat. Arch. Intl. Pharmacodyn. Thérap. 235(2):254–270.
  • Jonderko, G., Jonderko, K. and Gołab, T. (1989). Effect of somatostatin-14 on gastric emptying and on gastrin and insulin release after ingestion of a mixed solid-liquid meal in man. Mater. Med. Pol. 21(3):174–180.
  • Jones, I. R., Owens, D. R., Moody, A. J., Luzio, S. D., Morris, T. and Hayes, T. M. (1987). The effects of glucose-dependent insulinotropic polypeptide infused at physiological concentrations in normal subjects and type 2 (non-insulin-dependent) diabetic patients on glucose tolerance and B-cell secretion. Diabetologia. 30(9):707–712.
  • Joshi, S., Tough, I. R. and Cox, H. M. (2013). Endogenous PYY and GLP-1 mediate l-glutamine responses in intestinal mucosa. Br. J. Pharmacol. 170(5):1092–1101.
  • Julio-Pieper, M., O'Mahony, C. M., Clarke, G., Bravo, J. A., Dinan, T. G. and Cryan, J. F. (2012). Chronic stress-induced alterations in mouse colonic 5-HT and defecation responses are strain dependent. Stress. 15:218–226.
  • Kampmann, K., Ueberberg, S., Menge, B. A., Breuer, T. G. K., Uhl, W., Tannapfel, A. and Meier, J. J. (2016). Abundance and turnover of GLP-1 producing L-cells in ileal mucosa are not different in patients with and without type 2 diabetes. Metab.: Clin. Exp., 65(3):84–91.
  • Karlsson, F., Tremaroli, V., Nielsen, J. and Bäckhed, F. (2013a). Assessing the human gut microbiota in metabolic diseases. Diabetes. 62(10):3341–3349.
  • Karlsson, F.H., Tremaroli, V., Nookaew, I., et al. (2013b). Gut metagenome in European women with normal, impaired and diabeteic glucose control. Nature. 498:99–103.
  • Katsuki, A., Urakawa, H., Gabazza, E.C., Murashima, S., Nakatani, K., Togashi, K., Yano, Y., Adachi, Y. and Sumida, Y. (2004). Circulating levels of active ghrelin is associated with abdominal adiposity, hyperinsulinemia and insulin resistance in patients with type 2 diabetes mellitus. Eur. J. Endocrinol. 151(5):573–577.
  • Kim, S.-J., Nian, C., Karunakaran, S., Clee, S. M., Isales, C. M. and McIntosh, C. H. S. (2012). GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. PloS One. 7(7):e40156.
  • Kissileff, H. R., Pi-Sunyer, F. X., Thornton, J. and Smith, G. P. (1981). C-terminal octapeptide of cholecystokinin decreases food intake in man. Am. J. Clin. Nutr. 34(2):154–160.
  • Knop, F. K., Vilsboll, T., Madsbad, S., Holst, J. J., and Krarup, T. (2007). Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus. Diabetologia. 50: 797–805.
  • Kojima, M. (2005). Ghrelin: Structure and function. Physiol. Rev. 85(2):495–522.
  • Kootte, R. S, Vrieze, A., Holleman, F., Dallinga-Thie, G. M., Zoetendal, E. G., de Vos, W. M., Groen, A. K., Hoekstra, J. B., Stroes, E. S. and Nieuwdorp, M. (2012).The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus. Diab. Obes. Metab. 14(2):112–120.
  • Kreymann, B., Williams, G., Ghatei, M. A. and Bloom, S. R. (1987).Glucagon-like peptide-1 7–36: A physiological incretin in man. Lancet. 2(8571):1300–1304.
  • Kring, S. I., Werge, T., Holst, C., Toubro, S., Astrup, A., Hansen, T., Pedersen, O. and Sorensen, T. I. (2009). Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes. PLoS One. 4(8):e6696.
  • Larhammar, D. (1996). Evolution of neuropeptide Y, peptide YY and pancreatic polypeptide. Regulatory Peptides. 62(1):1–11.
  • Larsen, N., Vogensen, F. K., van den Berg, F. W., Nielsen, D. S., Andreasen, A. S., Pedersen, B. K., Al-Soud, W. A., Sørensen, S. J., Hansen, L. H. and Jakobsen, M. (2010).Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One. 5:e9085.
  • Lastya, A., Saraswati, M. R. and Suastika, K. (2014). The low level of glucagon-like peptide-1 (glp-1) is a risk factor of type 2 diabetes mellitus. BMC Res. Notes 7:849.
  • Lavine, J. A., Kibbe, C. R., Baan, M., Sirinvaravong, S., Umhoefer, H. M., Engler, K. A., and Davis, D. B. (2015). Cholecystokinin expression in the β-cell leads to increased β-cell area in aged mice and protects from streptozotocin-induced diabetes and apoptosis. Am. J. Physiol. Endocrinol. Metab. 309(10):E819–E828.
  • Lavine, J. A., Raess, P. W., Davis, D. B., Rabaglia, M. E., Presley, B. K., Keller, M. P. and Attie, A. D. (2008). Overexpression of pre-pro-cholecystokinin stimulates beta-cell proliferation in mouse and human islets with retention of islet function. Molec. Endocrinol. (Baltimore, Md.). 22(12):2716–2728.
  • Lavine, J. A., Raess, P. W., Stapleton, D. S., Rabaglia, M. E., Suhonen, J. I., Schueler, K. L., and Attie, A. D. (2010). Cholecystokinin is up-regulated in obese mouse islets and expands beta-cell mass by increasing beta-cell survival. Endocrinology. 151(8):3577–3588.
  • Le, T. K., Hosaka, T., Nguyen, T. T., Kassu, A., Dang, T. O., Tran, H. B, Pham, T. P., Tran, Q. B., Le, T. H., Pham, X. D. (2015). Bifidobacterium species lower serum glucose, increase expressions of insulin signaling proteins, and improve adipokine profile in diabetic mice. Biomed. Res. 36(1):63–70.
  • Lee, S., Yabe, D., Nohtomi, K., Takada, M., Morita, R., Seino, Y. and Hirano, T. (2010). Intact glucagon-like peptide-1 levels are not decreased in Japanese patients with type 2 diabetes. Endocr J. 57(2):119–126.
  • Legakis, I. N., Tzioras, C. and Phenekos, C. (2003). Decreased glucagon-like peptide 1 fasting levels in type 2 diabetes. Diabetes Care. 26(1):252.
  • Li, C., Li, X., Han, H., Cui, H., Peng, M., Wang, G. and Wang, Z. (2016). Effect of probiotics on metabolic profiles in type 2 diabetes mellitus: A meta-analysis of randomized, controlled trials. Medicine (Baltimore). 95(26):e4088.
  • Li, Y., Hansotia, T., Yusta, B., Ris, F., Halban, P. A. and Drucker, D. J. (2003). Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. J. Biol. Chem. 278(1):471–478.
  • Liddle, R. A., Rushakoff, R. J., Morita, E. T., Beccaria, L., Carter, J. D. and Goldfine, I. D. (1988). Physiological role for cholecystokinin in reducing postprandial hyperglycemia in humans. J. Clin. Invest. 81(6):1675–1681.
  • Lieverse, R. J., Jansen, J. B., Masclee, A. M. and Lamers, C. B. (1995). Effects of somatostatin on human satiety. Neuroendocrinology. 61(2):112–116.
  • Ling, Z., Wu, D., Zambre, Y., Flamez, D., Drucker, D. J., Pipeleers, D. G. and Schuit, F. C. (2001). Glucagon-like peptide 1 receptor signaling influences topography of islet cells in mice. Virchows Archiv. 438(4):382–387.
  • Little, T. J., Horowitz, M. and Feinle-Bisset, C. (2007). Modulation by high-fat diets of gastrointestinal function and hormones associated with the regulation of energy intake: Implications for the pathophysiology of obesity. Am. J. Clin. Nutr. 86(3):531–541.
  • Long, R. G., Christofides, N. D., Fitzpatrick, M. L., O'Shaughnessy, D. J. and Bloom, S. R. (1982). Effects of intravenous somatostatin and motilin on the blood glucose and hormonal response to oral glucose. Eur. J. Clin. Invest. 12(4):331–336.
  • Lopes, L. S., Schwartz, R. P., Ferraz-de-Souza, B., da Silva, M. E., Corrêa, P. H. and Nery, M. (2015). The role of enteric hormone GLP-2 in the response of bone markers to a mixed meal in postmenopausal women with type 2 diabetes mellitus. Diabetol Metab. Syndr. 7:13.
  • Lund, A., Vilsbøll, T., Bagger, J. I., Holst, J. J. and Knop, F. K. (2011). The separate and combined impact of the intestinal hormones, GIP, GLP-1, and GLP-2, on glucagon secretion in type 2 diabetes. Am. J. Physiol. Endocrinol Metab. 300(6):E1038–E1046.
  • Ma, H. T., Kato, M. and Tatemoto, K. (1996). Effects of pancreastatin and somatostatin on secretagogues-induced rise in intracellular free calcium in single rat pancreatic islet cells. Regulatory Peptides. 61(2):143–148.
  • Marco, J., Correas, I., Zulueta, M. A., Vincent, E., Coy, D. H., Comaru-Schally, A. M. and Schally, A. V., Rodríguez-Arnao, M. D., Gómez-Pan, A. (1983). Inhibitory effect of somatostatin-28 on pancreatic polypeptide, glucagon and insulin secretion in normal man. Horm Metab Res. 15(8):363–366.
  • Markianos, M., Evangelopoulos, M. E., Koutsis, G. and Sfagos, C. (2013). Elevated CSF serotonin and dopamine metabolite levels in overweight subjects. Obesity (Silver Spring). 21(6):1139–1142.
  • Marks, S. J., Moore, N. R., Clark, M. L., Strauss, B. J. and Hockaday, T. D.(1996). Reduction of visceral adipose tissue and improvement of metabolic indices: Effect of dexfenfluramine in NIDDM. Obes. Res. 4(1):1–7.
  • Matikainen, N., Björnson, E., Söderlund, S., Borén, C., Eliasson, B., Pietiläinen, K. H., Bogl, L. H., Hakkarainen, A., Lundbom, N., Rivellese, A., Riccardi, G., Després, J. P., Alméras, N., Holst, J. J., Deacon, C. F., Borén, J. and Taskinen, M. R. (2016). Minor contribution of endogenous GLP-1 and GLP-2 to postprandial lipemia in obese men. PLoS One. 11(1):e0145890.
  • Mazidi, M., Rezaie, P., Kengne, A. P., Mobarhan, M. G. and Ferns, G. A. (2016). Gut microbiome and metabolic syndrome. Diabetes Metab Syndr. 10(2–1):S150–S157.
  • Mefford, I. N., Mefford, J. T. and Burris, C. A. (2012). Improved diabetes control and pancreatic function in a type 2 diabetic after omeprazole administration. Case Reports in Endocrinology. 2012:468609.
  • Meier, J. J., Gallwitz, B., Schmidt, W. E. and Nauck, M. A.(2002). Glucagon-like peptide 1 as a regulator of food intake and body weight: Therapeutic perspectives. Eur. J. Pharmacol. 440(2–3):269–279.
  • Meier, J. J., Gallwitz, B., Siepmann, N., Holst, J. J., Deacon, C. F., Schmidt, W. E. and Nauck, M. A. (2003). Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia. 46(6):798–801.
  • Meier, J. J., Hücking, K., Holst, J. J., Deacon, C. F., Schmiegel, W. H. and Nauck, M. A. (2001). Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes. 50(11):2497–2504.
  • Meier, J. J., Nauck, M. A., Pott, A., Heinze, K., Goetze, O., Bulut, K., Schmidt, W. E., Gallwitz, B. and Holst, J. J. (2006). Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans. Gastroenterology. 130(1):44–54.
  • Meier, J. J., Gallwitz, B., Kask, B., Deacon, C. F., Holst, J. J., Schmidt, W. E. and Nauck, M. A. (2004). Stimulation of insulin secretion by intravenous bolus injection and continuous infusion of gastric inhibitory polypeptide in patients with type 2 diabetes and healthy control subjects. Diabetes. 53(3):S2204.
  • Migdalis, L., Thomaides, T., Chairopoulos, C., Kalogeropoulou, C., Charalabides, J. and Mantzara, F. (2001). Changes of gastric emptying rate and gastrin levels are early indicators of autonomic neuropathy in type II diabetic patients. Clin. Auton. Res. 11(4):259–263.
  • Milewicz, A., Mikulski, E. and Bidzińska, B. (2000). Plasma insulin, cholecystokinin, galanin, neuropeptide Y and leptin levels in obese women with and without type 2 diabetes mellitus. Int. J. Obes. Relat. Metab. Disord. 24(2):S152–S153.
  • Miyawaki, K., Yamada, Y., Ban, N., Ihara, Y., Tsukiyama, K., Zhou, H. and Seino, Y. (2002). Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nature Med. 8(7):738–742.
  • Miyazaki, K., Funakoshi, A. and Ibayashi, H. (1986).Plasma somatostatin-like immunoreactivity responses to a mixed meal and the heterogeneity in healthy and non-insulin-dependent (NIDDM) diabetics. Endocrinol Jpn. 33(1):51–59.
  • Monteleone, P., Piscitelli, F., Scognamiglio, P., Monteleone, A. M., Canestrelli, B., Di Marzo, V. and Maj, M. (2012). Hedonic eating is associated with increased peripheral levels of ghrelin and the endocannabinoid 2-arachidonoyl-glycerol in healthy humans: A pilot study. J. Clin. Endocrinol Metab. 97(6):E917–E924.
  • Mul, J. D., Begg, D. P., Barrera, J. G., Li, B., Matter, E. K., D'Alessio, D. A. and Sandoval, D. A. (2013). High-fat diet changes the temporal profile of GLP-1 receptor-mediated hypophagia in rats. Am. J. Physiol. Regul. Integr. Comparat. Physiol. 305(1):R68–R77.
  • Müller, T. D., Nogueiras, R., Andermann, M. L., Andrews, Z. B., Anker, S. D., Argente, J. and Tschöp, M. H. (2016). Ghrelin. Molec. Metab. 4(6):437–460.
  • Mumphrey, M. B., Patterson, L. M., Zheng, H. and Berthoud, H. R. (2013). Roux-en-Y gastric bypass surgery increases number but not density of CCK-, GLP-1-, 5-HT-, and neurotensin-expressing enteroendocrine cells in rats. Neurogastroenterol. Motility Off. J. Eur. Gastrointest. Motil. Soc. 25(1):e70–e79.
  • Nakano, I., Funakoshi, A., Shinozaki, H., Miyazaki, K., Ibayashi, H., Tateish, I. K. and Hamaoka. (1986). Thigh plasma cholecystokinin response following ingestion of test meal by patients with non-insulin dependent diabetes mellitus. Regul. Pept. 14(3):229–236.
  • Nam, J. S., Nam, J. Y., Yoo, J. S., Cho, M., Park, J. S., Ahn, C. W., … Lee, H. C. (2010). The effect of mosapride (5HT-4 receptor agonist) on insulin sensitivity and GLUT4 translocation. Diabetes Res. Clin. Pract. 87(3):329–334.
  • Natalicchio, A., De Stefano, F., Orlando, M. R., Melchiorre, M., Leonardini, A., Cignarelli, A. and Giorgino, F. (2010). Exendin-4 prevents c-Jun N-terminal protein kinase activation by tumor necrosis factor-alpha (TNFalpha) and inhibits TNFalpha-induced apoptosis in insulin-secreting cells. Endocrinology. 151(5):2019–2029.
  • Natalicchio, A., Labarbuta, R., Tortosa, F., Biondi, G., Marrano, N., Peschechera, A. and Giorgino, F. (2013). Exendin-4 protects pancreatic beta cells from palmitate-induced apoptosis by interfering with GPR40 and the MKK4/7 stress kinase signalling pathway. Diabetologia. 56(11):2456–2466.
  • Nauck, M., Stöckmann, F., Ebert, R. and Creutzfeldt, W. (1986). Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 29(1):46–52.
  • Nauck, M. A, Niedereichholz, U., Ettler, R., Holst, J. J., Orskov, C., Ritzel, R. and Schmiegel, W. H. (1997). Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am. J. Physiol. 273(5 Pt 1):E981–E988.
  • Nauck, M. A., Bartels, E., Orskov, C., Ebert, R. and Creutzfeldt, W. (1993). Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7–36) amide infused at near-physiological insulinotropic hormone and glucose concentrations. J. Clin. Endocrinol Metab. 76(4):912–917.
  • Nauck, M.A., Heimesaat, M.M., Orskov, C., Holst, J.J., Ebert, R. and Creutzfeldt, W.(1993). Preserved incretin activity of glucagon-like peptide 1 [7–36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J. Clin. Invest. 91(1):301–307.
  • Nauck, M. A., Kleine, N., Orskov, C., Holst, J. J., Willms, B. and Creutzfeldt, W. (1993). Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7–36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 36(8):741–744.
  • Neish, A. S. (2009). Microbes in gastrointestinal health and disease. Gastroenterology. 136: 65–80.
  • Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., et al. (2012). Host-gut microbiota metabolic interactions. Science. 336:1262–1267.
  • Omar, B., Ahlkvist, L., Yamada, Y., Seino, Y. and Ahrén, B. (2016). Incretin hormone receptors are required for normal beta cell development and function in female mice. Peptides. 79:58–65.
  • Orskov, C., Holst, J. J. and Nielsen, O. V. (1988). Effect of truncated glucagon-like peptide-1 [proglucagon-(78–107) amide] on endocrine secretion from pig pancreas, antrum, and nonantral stomach. Endocrinology. 123(4):2009–2013.
  • Pace, C. S. and Tarvin, J. T. (1981). Somatostatin: Mechanism of action in pancreatic islet beta-cells. Diabetes. 30(10):836–42.
  • Pace, C. S., Murphy, M., Conant, S. and Lacy, P. E. (1977). Somatostatin inhibition of glucose-induced electrical activity in cultured rat islet cells. Am. J. Physiol. 233(5):C165–C171.
  • Panwar, H., Rashmi, H. M., Batish, V. K., et al. (2013). Probiotics as potential biotherapeutics in the management of type 2 diabetes: Prospects and perspectives. Diab./Metab. Res. Rev. 29(2):103–112.
  • Pedersen, H. K., Gudmundsdottir, V., Nielsen, H. B., Hyotylainen, T., Nielsen, T., Jensen, B. A., Forslund, K., Hildebrand, F., Prifti, E., Falony, G., Le Chatelier, E., Levenez, F., Doré, J., Mattila, I., Plichta, D. R., Pöhö, P., Hellgren, L.I., Arumugam, M., Sunagawa, S., Vieira-Silva, S., Jørgensen, T, Holm, J. B., Trošt, K., Meta, HIT, Consortium, Kristiansen, K., Brix, S., Raes, J., Wang, J., Hansen, T., Bork, P., Brunak, S., Oresic, M., Ehrlich, S. D., Pedersen, O. (2016). Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 535(7612):376–381.
  • Pedersen, J., Ugleholdt, R. K., Jorgensen, S. M., Windeløv, J. A., Grunddal, K. V, Schwartz, T. W., Füchtbauer, E. M., Poulsen, S. S., Holst, P. J. and Holst, J. J. (2013). Glucose metabolism is altered after loss of L cells and α-cells but not influenced by loss of K cells. Am. J. Physiol. Endocrinol. Metab. 304:E60–E73.
  • Pestell, R. G., Crock, P. A., Ward, G. M., Alford, F. P., Best, J. D. (1989). Fenfluramine increases insulin action in patients with NIDDM. Diab. Care. 12(4):252–258.
  • Portela-Gomes, G. M., Grimelius, L., Westermark, P. and Stridsberg, M. (2010). Somatostatin receptor subtypes in human type 2 diabetic islets. Pancreas. 39(6):836–842.
  • Pöykkö, S. M., Kellokoski, E., Hörkkö, S., Kauma, H., Kesäniemi, Y. A. and Ukkola, O. (2003). Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes. 52(10):2546–2553.
  • Price, J. C., Kelley, D. E., Ryan, C. M., Meltzer, C. C., Drevets, W. C., Mathis, C. A., Mazumdar, S. and Reynolds, C. F. (2002). Evidence of increased serotonin-1A receptor binding in type 2 diabetes: A positron emission tomography study. Brain Res. 927(1):97–103.
  • Proietto, J., Thorburn, A. W., Fabris, S. and Harrison, L. C. (1994). Effects of dexfenfluramine on glucose turnover in non-insulin-dependent diabetes mellitus. Diabetes Res. Clin. Pract. 23(2):127–134.
  • Psichas, A., Sleeth, M. L., Murphy, K. G., Brooks, L., Bewick, G. A., Hanyaloglu, A. C. and Frost, G. (2015). The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int. J. Obesity. 39(3):424–429.
  • Qin, J., Li, Y., Cai, Z., et al. (2012).A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 490:55–60.
  • Rachman, J., Barrow, B. A., Levy, J. C. and Turner, R. C. (1997). Near-normalisation of diurnal glucose concentrations by continuous administration of glucagon-like peptide-1 (GLP-1) in subjects with NIDDM. Diabetologia. 40(2):205–211.
  • Rachman, J., Gribble, F. M., Barrow, B. A., Levy, J. C., Buchanan, K. D. and Turner, R. C.(1996). Normalization of insulin responses to glucose by overnight infusion of glucagon-like peptide 1 (7–36) amide in patients with NIDDM. Diabetes. 45(11):1524–1530.
  • Rehfeld, J. F. (1971). Effect of gastrin and its C-terminal tetrapeptide on insulin secretion in man. Acta Endocrinol (Copenh). 66(1):169–176.
  • Rehfeld, J. F. and Stadil, F. (1973). The effect of gastrin on basal- and glucose-stimulated insulin secretion in man. J. Clin. Invest. 52(6):1415–1426.
  • Rooman, I. and Bouwens, L. (2004). Combined gastrin and epidermal growth factor treatment induces islet regeneration and restores normoglycaemia in C57Bl6/J mice treated with alloxan. Diabetologia. 47(2):259–265.
  • Rubino, F., R'bibo, S. L., del Genio, F., Mazumdar, M. and McGraw, T. E. (2012). Metabolic surgery: The role of the gastrointestinal tract in diabetes mellitus. Nat. Rev. Endocrinol. 6(2):102–109.
  • Rubino, F., Zizzari, P., Tomasetto, C., Bluet-Pajot, M. T., Forgione, A., Vix, M. and Marescaux, J. (2005). The role of the small bowel in the regulation of circulating ghrelin levels and food intake in the obese Zucker rat. Endocrinology. 146(4):1745–1751.
  • Rushakoff, R. A., Goldfine, I. D., Beccaria, L. J., Mathur, A., Brand, R. J. and Liddle, R. A. (1993). Reduced postprandial cholecystokinin (CCK) secretion in patients with noninsulin-dependent diabetes mellitus: Evidence for a role for CCK in regulating postprandial hyperglycemia. J. Clin. Endocrinol. Metab. 76(2):489–493.
  • Rushakoff, R. J, Goldfine, I. D., Carter, J. D. and Liddle, R. A. (1987). Physiological concentrations of cholecystokinin stimulate amino acid-induced insulin release in humans. J. Clin. Endocrinol. Metab. 65(3):395–401.
  • Sarson, D. L., Wood, S. M., Kansal, P. C. and Bloom, S. R. (1984). Glucose-dependent insulinotropic polypeptide augmentation of insulin. Physiology or pharmacology?. Diabetes. 33(4):389–393.
  • Sasaki, S., Miyatsuka, T., Matsuoka, T., Takahara, M., Yamamoto, Y., Yasuda, T. and Shimomura, I. (2015). Activation of GLP-1 and gastrin signalling induces in vivo reprogramming of pancreatic exocrine cells into beta cells in mice. Diabetologia. 58(11):2582–2591.
  • Scheen, A. J., Paolisso, G., Salvatore, T., Lefèbvre, P. J. (1991). Improvement of insulin-induced glucose disposal in obese patients with NIDDM after 1-wk treatment with d-fenfluramine. Diabetes Care. 14(4):325–332.
  • Schirra, J., Houck, P., Wank, U., Arnold, R., Göke, B. and Katschinski, M. (2000). Effects of glucagon-like peptide-1(7–36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans. Gut. 46(5):622–631.
  • Schmidt, W. E., Siegel, E. G. and Creutzfeldt, W. (1985). Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets. Diabetologia. 28(9): 704–707.
  • Scrocchi, L. A., Hill, M. E., Saleh, J., Perkins, B. and Drucker, D. J. (2000). Elimination of glucagon-like peptide 1R signaling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action. Diabetes. 49(9):1552–1560.
  • Sekhar, M. S. and Unnikrishnan, M. K. (2015). Probiotic research for diabetes prevention. Nutrition. 31(1):248.
  • Shi, X., Zhou, F., Li, X., Chang, B., Li, D., Wang, Y. and Guan, X. (2013). Central GLP-2 enhances hepatic insulin sensitivity via activating PI3K signaling in POMC neurons. Cell Metab. 18(1):86–98.
  • Shi, Y.-C., Loh, K., Bensellam, M., Lee, K., Zhai, L., Lau, J. and Herzog, H. (2015). Pancreatic PYY is critical in the control of insulin secretion and glucose homeostasis in female mice. Endocrinology. 156(9):3122–3136.
  • Shimizu, H., Eldar, S., Heneghan, H. M., Schauer, P. R., Kirwan, J. P. and Brethauer, S. A. (2014). The effect of selective gut stimulation on glucose metabolism after gastric bypass in the Zucker diabetic fatty rat model. Surgery for obesity and related diseases. Off. J. Am. Soc. Bariatr. Surg. 10(1):29–35.
  • Singh, P. K., Hota, D., Dutta, P., Sachdeva, N., Chakrabarti, A., Srinivasan, A., Singh, I. and Bhansali, A. (2012). Pantoprazole improves glycemic control in type 2 diabetes: A randomized, double-blind, placebo-controlled trial. J. Clin. Endocrinol. Metab. 97(11):E2105–E2108.
  • Skrha, J., Hilgertová, J., Jarolímková, M., Kunešová, M. and Hill, M. (2010). Meal test for glucose-dependent insulinotropic peptide (GIP) in obese and type 2 diabetic patients. Physiol. Res. 59(5):749–755.
  • Song, I., Patel, O., Himpe, E., Muller, C. J. F. and Bouwens, L. (2015). Beta cell mass restoration in alloxan-diabetic mice treated with EGF and gastrin. PloS One. 10(10):e0140148.
  • Sorensen, L. B., Flint, A., Raben, A., Hartmann, B., Holst, J. J. and Astrup, A. (2003). No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects. J. Int. Assoc. Study Obesity. 27(4):450–456.
  • Starosel'tseva, L. K., Kniazeva, A. P., Belovalova, I. M. and Abduraimova, G. R. (1988).The role of gastrin in regulating insulin and glucagon secretion in patients with diabetes mellitus. Probl. Endokrinol (Mosk). 34(4):20–25.
  • Steiner, C., Othman, A., Saely, C. H., Rein, P., Drexel, H., von Eckardstein, A., Rentsch, K. M. (2011). Bile acid metabolites in serum: Intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus. PloS One. 6:e25006.
  • Steinert, R. E., Poller, B., Castelli, M. C., Drewe, J. and Beglinger, C. (2010). Oral administration of glucagon-like peptide 1 or peptide YY 3–36 affects food intake in healthy male subjects. Am. J. Clin. Nutr. 6(11):e25006.
  • Stenman, L. K., Waget, A., Garret, C., Klopp, P., Burcelin, R., Lahtinen, S. (2014). Potential probiotic Bifidobacterium animalis ssp. lactis 420 prevents weight gain and glucose intolerance in diet-induced obese mice. Benef Microbes. 5(4):437–445.
  • Stewart, G. O., Stein, G. R., Davis, T. M. and Findlater, P. (1993). Dexfenfluramine in type II diabetes: Effect on weight and diabetes control. Med. J. Aust. 158(3):167–169.
  • Strowski, M. Z., Parmar, R. M., Blake, A. D. and Schaeffer, J. M. (2000). Somatostatin inhibits insulin and glucagon secretion via two receptors subtypes: An in vitro study of pancreatic islets from somatostatin receptor 2 knockout mice. Endocrinology. 141(1):111–117.
  • Suarez-Pinzon, W. L., Power, R. F., Yan, Y., Wasserfall, C., Atkinson, M. and Rabinovitch, A. (2008). Combination therapy with glucagon-like peptide-1 and gastrin restores normoglycemia in diabetic NOD mice. Diabetes. 57(12):3281–3288.
  • Sun, Y., Asnicar, M., Saha, P. K., Chan, L. and Smith, R. G. (2006). Ablation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice. Cell Metab. 3(5):379–386.
  • Tamborlane, W. V., Sherwin, R. S., Hendler, R. and Felig, P. (1977). Metabolic effects of somatostatin in maturity-onset diabetes. N. Engl. J. Med. 297(4):181–183.
  • Tatarkiewicz, K., Hargrove, D. M., Jodka, C. M., Gedulin, B. R., Smith, P. A., Hoyt, J. A., and Parkes, D. G. (2014). A novel long-acting glucose-dependent insulinotropic peptide analogue: Enhanced efficacy in normal and diabetic rodents. Diab. Obes. Metab. 16(1):75–85.
  • Tellez, N. and Montanya, E. (2014). Gastrin induces ductal cell dedifferentiation and beta-cell neogenesis after 90% pancreatectomy. J. Endocrinol. 223(1):67–78.
  • Tellez, N., Joanny, G., Escoriza, J., Vilaseca, M. and Montanya, E. (2011). Gastrin treatment stimulates beta-cell regeneration and improves glucose tolerance in 95% pancreatectomized rats. Endocrinology. 152(7):2580–2588.
  • Terry, N. A., Walp, E. R., Lee, R. A., Kaestner, K. H. and May, C. L. (2014). Impaired enteroendocrine development in intestinal-specific Islet1 mouse mutants causes impaired glucose homeostasis. Am. J. Physiol. Gastrointest. Liver Physiol. 307(10):G979–G991.
  • Toft-Nielsen, M. B., Damholt, M. B., Madsbad, S., Hilsted, L. M., Hughes, T. E., Michelsen, B. K. and Holst, J. J. (2001). Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J. Clin. Endocrinol. Metab. 86(8):3717–3723.
  • Tong, J., Prigeon, R. L., Davis, H. W., Bidlingmaier, M., Kahn, S. E., Cummings, D. E. and D'Alessio, D. (2010). Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans. Diabetes. 59(9):2145–2151.
  • Trimble, E. R., Gerber, P. P. and Renold, A. E. (1981). Abnormalities of pancreatic somatostatin secretion corrected by in vivo insulin treatment of streptozotocin-diabetic rats. Diabetes. 30(10):865–867.
  • Turnbaugh, P. J, Ridaura, V. K., Faith, J. J., Rey, F. E., Knight, R. and Gordon, J. I. (2009). The effect of diet on the human gut microbiome: A metagenomic analysis in humanized gnotobiotic mice. Sci. Transl. Med. 1(6):6–14.
  • Turnbaugh, P. J., B¨ ackhed, F., Fulton, L. and Gordon, J. I. (2008). Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host. Microbe. 3:213–223.
  • Ueno, H., Shiiya, T., Mizuta, M., Mondal, S. M. and Nakazato, M. (2007). Plasma ghrelin concentrations in different clinical stages of diabetic complications and glycemic control in Japanese diabetics. Endocr. J. 54(6):895–902.
  • Ueno, N., Inui, A., Asakawa, A., Takao, F., Komatsu, Y., Kotani, K. and Kasuga, M. (2002). Mosapride, a 5HT-4 receptor agonist, improves insulin sensitivity and glycaemic control in patients with Type II diabetes mellitus. Diabetologia. 45(6):792–797.
  • Ukkola, O. H., Puurunen, V. P., Piira, O. P., Niva, J. T., Lepojärvi, E. S., Tulppo, M. P. and Huikuri, H. V. (2011). High serum fasting peptide YY (3–36) is associated with obesity-associated insulin resistance and type 2 diabetes. Regul. Pept. 170(1–3):38–42.
  • Urbano, F., Filippello, A., Di Pino, A., Barbagallo, D., Di Mauro, S., Pappalardo, A. and Piro, S. (2016). Altered expression of uncoupling protein 2 in GLP-1-producing cells after chronic high glucose exposure: Implications for the pathogenesis of diabetes mellitus. Am. J. Physiol. Cell Physiol. 310(7):C558–C567.
  • Utzschneider, K. M., Kratz, M., Damman, C. J. and Hullarg, M. (2016).Mechanisms linking the gut microbiome and glucose metabolism. J. Clin. Endocrinol. Metab. 101(4):1445–1454.
  • Vamvini, M. T., Hamnvik, O.-P., Sahin-Efe, A., Gavrieli, A., Dincer, F., Farr, O. M. and Mantzoros, C. S. (2016). Differential effects of oral and intravenous lipid administration on key molecules related to energy homeostasis. J. Clin. Endocrinol. Metab. 101(5):1989–1997.
  • Vella, A. (2013). Enteroendocrine secretion after Roux-en-Y gastric bypass: Is it important? Neurogastroenterology and motility. Off. J. Eur. Gastrointestinal Motil. Soc. 25(1):1–3.
  • Vilsboll, T., Krarup, T., Deacon, C. F., Madsbad, S. and Holst, J. J. (2001). Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 50(3):609–613.
  • Vilsboll, T., Krarup, T., Madsbad, S. and Holst, J.J. (2002). Defective amplification of the late phase insulin response to glucose by GIP in obese type II diabetic patients. Diabetologia. 45:1111–1119.
  • Vincent, R. P., Omar, S., Ghozlan, S., Taylor, D. R., Cross, G., Sherwood, R. A., Fandriks, L., Olbers, T., Werling, M., Alaghband-Zadeh, J., le Roux, C. W.(2013). Higher circulating bile acid concentrations in obese patients with type 2 diabetes. Ann. Clin. Biochem. 50(Pt 4):360–364.
  • Vrieze, A., Van Nood, E., Holleman, F., Salojarvi, J., Kootte, R. S., Bartelsman, J. F., et al. (2012). Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 143(4):913–916.e7.
  • Ward, F. R., Leblanc, H. and Yen, S. S. (1977). The inhibitory effect of somatostatin on growth hormone, insulin and glucagon secretion in diabetes mellitus. J. Clin. Endocrinol Metab. 41(3):527–532.
  • Weintraub, M., Sundaresan, P. R., Madan, M., Schuster, B., Balder, A., Lasagna, L. and Cox, C. (1992). Long-term weight control study. I (weeks 0 to 34). The enhancement of behavior modification, caloric restriction, and exercise by fenfluramine plus phentermine versus placebo. Clin. Pharmacol. Ther. 51(5):586–594.
  • Weltzin, T. E., Fernstrom, M. H., Fernstrom, J. D., Neuberger, S. K. and Kaye, W. H. (1995). Acute tryptophan depletion and increased food intake and irritability in bulimia nervosa. Am. J. Psychiatry. 152(11):1668–1671.
  • Wettergren, A., Schjoldager, B., Mortensen, P. E., Myhre, J., Christiansen, J. and Holst, J. J.(1993). Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig. Dis. Sci. 38(4):665–673.
  • Widenmaier, S. B., Kim, S.-J., Yang, G. K., De Los Reyes, T., Nian, C., Asadi, A. and McIntosh, C. H. S. (2010). A GIP receptor agonist exhibits β-cell anti-apoptotic actions in rat models of diabetes resulting in improved β-cell function and glycemic control. Plos One. 5(3):e9590.
  • Williams, D. L., Hyvarinen, N., Lilly, N., Kay, K., Dossat, A., Parise, E. and Torregrossa, A.M. (2011). Maintenance on a high-fat diet impairs the anorexic response to glucagon-like-peptide-1 receptor activation. Physiology Behavior. 103(5):557–564.
  • Willms, B., Werner, J., Holst, J. J., Orskov, C., Creutzfeldt, W. and Nauck, M. A. (1996). Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: Effects of exogenous glucagon-like peptide-1 (GLP-1)-(7–36) amide in type 2 (noninsulin-dependent) diabetic patients. J. Clin. Endocrinol. Metab. 81(1):327–332.
  • Wozniak, K. M. 1., Linnoila, M. (1991). Hyperglycemic properties of serotonin receptor antagonists. Life Sci. 49(2):101–109.
  • Wren, A. M., Seal, L. J., Cohen, M. A., Brynes, A. E., Frost, G. S., Murphy, K. G., Dhillo, W. S., Ghatei, M. A. and Bloom, S. R. (2001). Ghrelin enhances appetite and increases food intake in humans. J. Clin. Endocrinol Metab. 86(12):5992.
  • Wright, M., Woodrow, G., O'Brien, S., Armstrong, E., King, N., Dye, L., Blundell, J., Brownjohn, A. and Turney, J. (2004). Cholecystokinin and leptin: Their influence upon the eating behaviour and nutrient intake of dialysis patients. Nephrol. Dial. Transplant. 19(1):133–140.
  • Yabe, D. and Seino, Y. (2011). Two incretin hormones GLP-1 and GIP: Comparison of their actions in insulin secretion and β cell preservation. Progress Biophys. Mol. Biol. 107(2):248–256.
  • Yakovlieva, M., Tacheva, T., Mihaylova, S., Tropcheva, R., Trifonova, K., Toleкova, A., Danova, S. and Vlaykova, T. (2015). Influence of Lactobacillus brevis 15 and Lactobacillus plantarum 13 on blood glucose and body weight in rats after high-fructose diet. Benef. Microbes. 6(4):505–512.
  • Zhang, S., Wang, S., Hyrc, K. and Wice, B. M. (2013). Metabolic profiling identifies beta-hydroxypyruvate (HP) as a potential mediator of type 2 diabetes mellitus (T2DM) in mice. Diabetes. 62: A524.
  • Zhang, S., Wang, S., Puhl, M. D., Jiang, X., Hyrc, K. L., Laciny, E., Wallendorf, M. J., Pappan, K. L., Coyle, J. T. and Wice, B. M. (2015). Global biochemical profiling identifies β-hydroxypyruvate as a potential mediator of type 2 diabetes in mice and humans. Diabetes. 64:1383–1394.
  • Zhang, Y., Ying, B., Shi, L., Fan, H., Yang, D., Xu, D. and Wen, F. (2007). Ghrelin inhibit cell apoptosis in pancreatic beta cell line HIT-T15 via mitogen-activated protein kinase/phosphoinositide 3-kinase pathways. Toxicology. 237(1–3):194–202.

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