Dual SGLT1/SGLT2 Inhibitor Phlorizin Ameliorates Non-Alcoholic Fatty Liver Disease and Hepatic Glucose Production in Type 2 Diabetic Mice

References

• Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006;43:S99–S112. doi:10.1002/hep.20973
   PubMed Web of Science ®Google Scholar
• Tevar AD, Clarke C, Wang J, et al. Clinical review of nonalcoholic steatohepatitis in liver surgery and transplantation. J Am Coll Surg. 2010;210:515–526. doi:10.1016/j.jamcollsurg.2010.01.020
   PubMedGoogle Scholar
• Zafrani ES. Non-alcoholic fatty liver disease: an emerging pathological spectrum. Virchows Arch. 2004;444:3–12. doi:10.1007/s00428-003-0943-7
   PubMed Web of Science ®Google Scholar
• Brunt EM. Pathology of nonalcoholic steatohepatitis. Hepatol Res. 2005;33:68–71. doi:10.1016/j.hepres.2005.09.006
   PubMed Web of Science ®Google Scholar
• Safaei A, Arefi Oskouie A, Mohebbi SR, et al. Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases. Gastroenterol Hepatol Bed Bench. 2016;9:158–173.
   PubMedGoogle Scholar
• Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology. 1990;11:74–80. doi:10.1002/hep.1840110114
   PubMed Web of Science ®Google Scholar
• Wieckowska A, McCullough AJ, Feldstein AE. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology. 2007;46:582–589. doi:10.1002/hep.21768
   PubMed Web of Science ®Google Scholar
• Firneisz G. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age? World J Gastroenterol. 2014;20:9072–9089. doi:10.3748/wjg.v20.i27.9072
   PubMed Web of Science ®Google Scholar
• Chitturi S, Abeygunasekera S, Farrell GC, et al. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology. 2002;35:373–379. doi:10.1053/jhep.2002.30692
   PubMed Web of Science ®Google Scholar
• Thorens B. GLUT2, glucose sensing and glucose homeostasis. Diabetologia. 2015;58(2):221–232. doi:10.1007/s00125-014-3451-1
   PubMed Web of Science ®Google Scholar
• De Fronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004;88:787–835. doi:10.1016/j.mcna.2004.04.013
   PubMedGoogle Scholar
• DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab. 2012;14:5–14. doi:10.1111/j.1463-1326.2011.01511.x
   PubMed Web of Science ®Google Scholar
• Rieg T, Vallon V. Development of SGLT1 and SGLT2 inhibitors. Diabetologia. 2018;61:2079–2086. doi:10.1007/s00125-018-4654-7
   PubMed Web of Science ®Google Scholar
• Hayashizaki-Someya Y, Kurosaki E, Takasu T, et al. Ipragliflozin, an SGLT2 inhibitor, exhibits a prophylactic effect on hepatic steatosis and fibrosis induced by choline-deficient l-amino acid-defined diet in rats. Eur J Pharmacol. 2015;754:19–24. doi:10.1016/j.ejphar.2015.02.009
   PubMed Web of Science ®Google Scholar
• Honda Y, Imajo K, Kato T, et al. The selective SGLT2 inhibitor ipragliflozin has a therapeutic effect on nonalcoholic steatohepatitis in mice. PLoS One. 2016;11:e0146337. doi:10.1371/journal.pone.0146337
   PubMed Web of Science ®Google Scholar
• Jojima T, Tomotsune T, Iijima T, Akimoto K, Suzuki K, Aso Y. Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes. Diabetol Metab Syndr. 2016;8:45. doi:10.1186/s13098-016-0169-x
   PubMed Web of Science ®Google Scholar
• Nakano S, Katsuno K, Isaji M, et al. Remogliflozin etabonate improves fatty liver disease in diet-induced obese male mice. J Clin Exp Hepatol. 2015;5:190–198. doi:10.1016/j.jceh.2015.02.005
   PubMedGoogle Scholar
• Nishimura N, Kitade M, Noguchi R, et al. Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, ameliorates the development of liver fibrosis in diabetic Otsuka Long-Evans Tokushima fatty rats. J Gastroenterol. 2016;51:1141–1149. doi:10.1007/s00535-016-1200-6
   PubMed Web of Science ®Google Scholar
• Qiang S, Nakatsu Y, Seno Y, et al. Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus. Diabetol Metab Syndr. 2015;7:104. doi:10.1186/s13098-015-0102-8
   PubMed Web of Science ®Google Scholar
• Komiya C, Tsuchiya K, Shiba K, et al. Ipragliflozin improves hepatic steatosis in obese mice and liver dysfunction in type 2 diabetic patients irrespective of body weight reduction. PLoS One. 2016;11:e0151511. doi:10.1371/journal.pone.0151511
   PubMed Web of Science ®Google Scholar
• Yonamine CY, Pinheiro-Machado E, Michalani ML, et al. Resveratrol improves glycemic control in type 2 diabetic obese mice by regulating glucose transporter expression in skeletal muscle and liver. Molecules. 2017;22:pii: E1180.
   PubMedGoogle Scholar
• Freitas HS, D’Agord Schaan B, da Silva RS, Okamoto MM, Oliveira-Souza M, Machado UF. Insulin but not phlorizin treatment induces a transient increase in GLUT2 gene expression in the kidney of diabetic rats. Nephron Physiol. 2007;105:42–51. doi:10.1159/000098442
   Web of Science ®Google Scholar
• Yonamine CY, Pinheiro-Machado E, Michalani ML, et al. Resveratrol improves glycemic control in insulin-treated diabetic rats: participation of the hepatic territory. Nutr Metab. 2016;13:44. doi:10.1186/s12986-016-0103-0
   Google Scholar
• David-Silva A, Freitas HS, Okamoto MM, Sabino-Silva R, Schaan BD, Machado UF. Hepatocyte nuclear factors 1α/4α and forkhead box A2 regulate the solute carrier 2A2 (Slc2a2) gene expression in the liver and kidney of diabetic rats. Life Sci. 2013;93:805–813. doi:10.1016/j.lfs.2013.10.011
   PubMedGoogle Scholar
• Freitas HS, Schaan BD, David-Silva A, et al. SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1alpha and HNF-3beta. Mol Cell Endocrinol. 2009;305:63–70. doi:10.1016/j.mce.2009.02.014
   PubMedGoogle Scholar
• Brunt EM. Nonalcoholic fatty liver disease: pros and cons of histologic systems of evaluation. Int J Mol Sci. 2016;17:pii: E97. doi:10.3390/ijms17010097
   PubMedGoogle Scholar
• Olney JW. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science. 1969;164:719–721. doi:10.1126/science.164.3880.719
   PubMed Web of Science ®Google Scholar
• Machado UF, Shimizu I, Saito M. Reduced content and preserved translocation of glucose transporter (GLUT 4) in white adipose tissue of obese mice. Physiol Behav. 1994;55:621–625. doi:10.1016/0031-9384(94)90035-3
   PubMedGoogle Scholar
• de Carvalho Papa P, Vargas AM, da Silva JL, Nunes MT, Machado UF. GLUT4 protein is differently modulated during development of obesity in monosodium glutamate-treated mice. Life Sci. 2002;71:1917–1928. doi:10.1016/S0024-3205(02)01948-3
   PubMedGoogle Scholar
• Ideta T, Shirakami Y, Miyazaki T, et al. The dipeptidyl peptidase-4 inhibitor teneligliptin attenuates hepatic lipogenesis via AMPK activation in non-alcoholic fatty liver disease model mice. Int J Mol Sci. 2015;16:29207–29218. doi:10.3390/ijms161226156
   PubMed Web of Science ®Google Scholar
• Miyazaki T, Shirakami Y, Kubota M, et al. Sodium alginate prevents progression of non-alcoholic steatohepatitis and liver carcinogenesis in obese and diabetic mice. Oncotarget. 2016;7:10448–10458. doi:10.18632/oncotarget.7249
   PubMedGoogle Scholar
• Nakanishi Y, Tsuneyama K, Fujimoto M, et al. Monosodium glutamate (MSG): a villain and promoter of liver inflammation and dysplasia. J Autoimmun. 2008;30:42–50. doi:10.1016/j.jaut.2007.11.016
   PubMed Web of Science ®Google Scholar
• Sasaki Y, Suzuki W, Shimada T, et al. Dose dependent development of diabetes mellitus and non-alcoholic steatohepatitis in monosodium glutamate-induced obese mice. Life Sci. 2009;85:490–498. doi:10.1016/j.lfs.2009.07.017
   PubMed Web of Science ®Google Scholar
• Yonamine CY, Alves-Wagner AB, Esteves JV, et al. Diabetes induces tri-methylation at lysine 9 of histone 3 at Slc2a4 gene in skeletal muscle: a new target to improve glycemic control. Mol Cell Endocrinol. 2019;481:26–34. doi:10.1016/j.mce.2018.11.006
   PubMedGoogle Scholar
• Rankin Fujimoto MM, Kushner JA. Adaptive beta-cell proliferation is severely restricted with advanced age. Diabetes. 2009;58:1365–1372. doi:10.2337/db08-1198
   PubMedGoogle Scholar
• Agius L. Glucokinase and molecular aspects of liver glycogen metabolism. Biochem J. 2008;414:1–18. doi:10.1042/BJ20080595
   PubMed Web of Science ®Google Scholar
• Fujimoto M, Tsuneyama K, Nakanishi Y, et al. A dietary restriction influences the progression but not the initiation of MSG-induced nonalcoholic steatohepatitis. J Med Food. 2014;17:374–383. doi:10.1089/jmf.2012.0029
   PubMedGoogle Scholar
• Tsuneyama K, Nishitsuji K, Matsumoto M, et al. Animal models for analyzing metabolic syndrome-associated liver diseases. Pathol Int. 2017;67:539–546. doi:10.1111/pin.12600
   PubMed Web of Science ®Google Scholar
• van der Heijden RA, Sheedfar F, Morrison MC, et al. High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice. Aging. 2015;7:256–268. doi:10.18632/aging.100738
   PubMedGoogle Scholar
• Brunt EM, Neuschwander-Tetri BA, Oliver D, Wehmeier KR, Bacon BR. Nonalcoholic steatohepatitis: histologic features and clinical correlations with 30 blinded biopsy specimens. Hum Pathol. 2004;35:1070–1082. doi:10.1016/j.humpath.2004.04.017
   PubMed Web of Science ®Google Scholar
• Watt MJ, Miotto PM, De Nardo W, Montgomery MK. The liver as an endocrine organ- linking NAFLD and insulin resistance. Endocr Rev. 2019;40:1367–1393. pii:er.2019–00034.
   PubMed Web of Science ®Google Scholar
• Gorgani-Firuzjaee S, Meshkani R. SH2 domain-containing inositol 5-phosphatase (SHIP2) inhibition ameliorates high glucose-induced de-novo lipogenesis and VLDL production through regulating AMPK/mTOR/SREBP1 pathway and ROS production in HepG2 cells. Free Radic Biol Med. 2015;89:679–689. doi:10.1016/j.freeradbiomed.2015.10.036
   PubMed Web of Science ®Google Scholar
• Yanuka-Kashles O, Cohen H, Trus M, Aran A, Benvenisty N, Reshef L. Transcriptional regulation of the phosphoenolpyruvate carboxykinase gene by cooperation between hepatic nuclear factors. Mol Cell Biol. 1994;14:7124–7133. doi:10.1128/MCB.14.11.7124
   PubMedGoogle Scholar
• Aso Y, Kato K, Sakurai S, et al. Impact of dapagliflozin, an SGLT2 inhibitor, on serum levels of soluble dipeptidyl peptidase-4 in patients with type 2 diabetes and non-alcoholic fatty liver disease. Int J Clin Pract. 2019;73:e13335. doi:10.1111/ijcp.13335
   PubMed Web of Science ®Google Scholar
• Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124:499–508. doi:10.1172/JCI72227
   PubMed Web of Science ®Google Scholar
• Merovci A, Solis-Herrera C, Daniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014;124:509–514. doi:10.1172/JCI70704
   PubMed Web of Science ®Google Scholar
• Bonner C, Kerr-Conte J, Gmyr V, et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med. 2015;21:512–517. doi:10.1038/nm.3828
   PubMed Web of Science ®Google Scholar
• Kuhre RE, Ghiasi SM, Adriaenssens AE, et al. No direct effect of SGLT2 activity on glucagon secretion. Diabetologia. 2019;62:1011–1023. doi:10.1007/s00125-019-4849-6
   PubMed Web of Science ®Google Scholar
• Yamazaki Y, Usui I, Kanatani Y, et al. Treatment with SRT1720, a SIRT1 activator, ameliorates fatty liver with reduced expression of lipogenic enzymes in MSG mice. Am J Physiol Endocrinol Metab. 2009;297:E1179–86. doi:10.1152/ajpendo.90997.2008
   PubMedGoogle Scholar