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Review Articles

Prominent and emerging anti-diabetic molecular targets

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Pages 491-506 | Received 25 Aug 2020, Accepted 01 Dec 2020, Published online: 18 Dec 2020

References

  • World Health Organization. Global status report on alcohol and health 2018. Washington (DC); 2019.
  • Saeedi P, Petersohn I, Salpea P, et al.; IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843.
  • Kerru N, Singh-PillayPaul A, Awolade P, et al. Current anti-diabetic agents and their molecular targets: A review. Eur J Med Chem. 2018;152:436–488.
  • Sargsyan A, Herman M. Regulation of glucose production in the pathogenesis of type 2 Diabetes. Curr Diab Rep. 2019;19(9):77.
  • Moller DE, Kaufman KD. Metabolic syndrome: a clinical and molecular perspective. Annu Rev Med. 2005;56:45–62.
  • Menting JG, Whittaker J, Margetts MB, et al. How insulin engages its primary binding site on the insulin receptor. Nature. 2013;493(7431):241–245.
  • Kadowaki T, Ueki K, Yamauchi T, et al. SnapShot: Insulin signaling pathways. Cell. 2012;148(3):624–624.e1.
  • Apostolova N, Iannantuoni F, Gruevska A, et al. Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions. Redox Biol. 2020;34:101517.
  • Zhang L, Chen Q, Li L, et al. Alpha-glucosidase inhibitors and hepatotoxicity in type 2 diabetes: a systematic review and meta-analysis. Sci Rep. 2016;6:32649.
  • Hedrington MS, Davis SN. Considerations when using alpha-glucosidase inhibitors in the treatment of type 2 diabetes. Expert Opin Pharmacother. 2019;20(18):2229–2235.
  • Derosa G, Maffioli P. α-Glucosidase inhibitors and their use in clinical practice. Arch Med Sci. 2012;8(5):8:899–906.
  • Kumar RV, Sinha VR. Newer insights into the drug delivery approaches of α-glucosidase inhibitors. Expert Opin Drug Deliv. 2012;9(4):403–416.
  • Deacon CF. Physiology and pharmacology of DPP-4 in glucose homeostasis and the treatment of type 2 diabetes. Front Endocrinol. 2019;10:80.
  • Szeto V, Chen N, Sun H, et al. The role of KATP channels in cerebral ischemic stroke and diabetes. Acta Pharmacol Sin. 2018;39(5):683–694. doi.org/10.1038/aps.2018.10
  • Tabassum A, Mahboob T. Role of peroxisome proliferator-activated receptor-gamma activation on visfatin, advanced glycation end products, and renal oxidative stress in obesity-induced type 2 diabetes mellitus. Hum Exp Toxicol. 2018;37(11):1187–1198. doi.: 10.1177/0960327118757588
  • Morita H, Deguchi J, Motegi Y, et al. Cyclic diarylheptanoids as Na+-glucose cotransporter (SGLT) inhibitors from Acer nikoense. Bioorg Med Chem Lett. 2010;20(3):1070–1074.
  • Abdul-Ghani MA, DeFronzo RA, Norton L. Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30-50% of filtered glucose load in humans. Diabetes. 2013;62(10):3324–3328.
  • DeFronzo RA. Bromocriptine: a sympatholytic, d2-dopamine agonist for the treatment of type 2 diabetes. Diabetes Care. 2011;34(4):789–794.
  • Mohamed L, Jaipaul S, Hameed R, et al. Mechanism of the beneficial and protective effects of exenatide in diabetic rats. J Endocrinol. 2014;220:291–304.
  • Deng X, Tavallaie MS, Sun R, et al. Drug discovery approaches targeting the incretin pathway. Bioorg Chem. 2020;99:103810.
  • Lebovitz HE. New treatments of diabetes: the β-amylin agonists. Annales D'Endocrinologie. 2008;69(2):147–150.
  • Bakke J, Haj FG. Protein-tyrosine phosphatase 1B substrates and metabolic regulation. Semin Cell Dev Biol. 2015;37:58–65.
  • Vieira MNN, Lyra E, Silva N, Ferreira ST, et al. Protein tyrosine phosphatase 1B (PTP1B): a potential target for alzheimer's therapy? Front Aging Neurosci. 2017;9:7.
  • Sharma B, Xie L, Yang F, et al. Recent advance on PTP1B inhibitors and their biomedical applications. Eur J Med Chem. 2020;199:112376.
  • Krishnan N, Konidaris KF, Gasser G, et al. A potent, selective, and orally bioavailable inhibitor of the protein-tyrosine phosphatase PTP1B improves insulin and leptin signaling in animal models. J Biol Chem. 2018;293(5):1517–1525.
  • Abdelsalam SS, Korashy HM, Zeidan A, et al. The Role of Protein Tyrosine Phosphatase (PTP)-1B in cardiovascular disease and its interplay with insulin resistance. Biomolecules. 2019;9:286.
  • Chung SSM, Ho ECM, Lam KSL, et al. Contribution of polyol pathway to diabetes-induced oxidative stress. J Am Soc Nephrol. 2003;14(8 Suppl 3):S233–S236.
  • Yabe-Nishimura C. Aldose reductase in glucose toxicity: a potential target for the Prevention of diabetic complications. Pharmacol Rev. 1998;50(1):21–33.
  • Behl T, Kaur I, Kotwani A. Implication of oxidative stress in progression of diabetic retinopathy. Surv Ophthalmol. 2016;61(2):187–196.
  • Dowarah J, Singh VP. Anti-diabetic drugs recent approaches and advancements. Bioorg Med Chem. 2020;28(5):115263.
  • Alexiou P, Pegklidou K, Chatzopoulou M, et al. Aldose reductase enzyme and its implication to major health problems of the 21st century. CMC. 2009;16(6):734–752.
  • Zhang T, Wang S, Lin Y, et al. Acetylation negatively regulates glycogen phosphorylase by recruiting protein phosphatase 1. Cell Metab. 2012;15(1):75–87.
  • Hayes JM, Kantsadi AL, Leonidas DD. Natural products and their derivatives as inhibitors of glycogen phosphorylase: potential treatment for type 2 diabetes. Phytochem Rev. 2014;13(2):471–498.
  • Donnier-Maréchal M, Vidal S. Glycogen phosphorylase inhibitors: a patent review (2013 - 2015). Expert Opin Ther Pat. 2016;26(2):199–212.
  • Hunter RW, Hughey CC, Lantier L, et al. Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase. Nat Med. 2018;24(9):1395–1406. 2018/08/27:
  • Kaur R, Dahiya L, Kumar M. Fructose-1, 6-bisphosphatase inhibitors: a new valid approach for management of type 2 diabetes mellitus. Eur J Med Chem. 2017;141:473–505.
  • Singh S, Harmalkar DS, Choi Y, et al. Fructose-1, 6-bisphosphatase Inhibitors: A Review of Recent (2000-2017) Advances and Structure-Activity Relationship Studies. Curr Med Chem. 2019;26(29):5542–5563.
  • Furukawa F, Tseng YC, Liu ST, et al. Induction of phosphoenolpyruvate carboxykinase (PEPCK) during acute acidosis and its role in acid secretion by V-ATPase-expressing ionocytes. Int J Biol Sci. 2015;11(6):712–725.
  • Sharma R, Kumari M, Prakash P, et al. Phosphoenolpyruvate carboxykinase in urine exosomes reflect impairment in renal gluconeogenesis in early insulin resistance and diabetes. Am J Physiol Renal Physiol. 2020;318(3):F720–F731.
  • Montori-Grau M, Tarrats N, Osorio-Conles O, et al. Glucose dependence of glycogen synthase activity regulation by GSK3 and MEK/ERK inhibitors and angiotensin-(1-7) action on these pathways in cultured human myotubes. Cell Sig. 2013;25(5):1318–1327.
  • Yucel G, Oro AE. Cell migration: GSK3β steers the cytoskeleton's tip. Cell. 2011;144(3):319–321.
  • Liu X, Yao Z. Chronic over-nutrition and dysregulation of GSK3 in diseases. Nutr Metab (Lond)). 2016;13:49.
  • Grimes CA, Jope RS. The multifaceted roles of glycogen synthase kinase 3β in cellular signaling. Prog Neurobiol. 2001;65(4):391–426.
  • Noori MS, Bhatt PM, Courreges MC, et al. Identification of a novel selective and potent inhibitor of glycogen synthase kinase-3. Am J Physiol Cell Physiol. 2019;317(6):C1289–C1303.
  • Ramurthy S, Pfister KB, Boyce RS, et al. Discovery and optimization of novel pyridines as highly potent and selective glycogen synthase kinase 3 inhibitors. Bioorg Med Chem Lett. 2020;30(4):126930.
  • Abedinzade M, Rostampour M, Mirzajani E, et al. Urtica dioica and Lamium album decrease glycogen synthase kinase-3 beta and increase K-Ras in diabetic rats. J Pharmacopuncture. 2019;22:248–252.
  • Stimson RH, Andrew R, McAvoy NC, et al. Increased whole-body and sustained liver cortisol regeneration by 11beta-hydroxysteroid dehydrogenase type 1 in obese men with type 2 diabetes provides a target for enzyme inhibition. Diabetes. 2011;60(3):720–725.
  • Dube S, Norby BJ, Pattan V, et al. 11β-hydroxysteroid dehydrogenase types 1 and 2 activity in subcutaneous adipose tissue in humans: implications in obesity and diabetes. J Clin Endocrinol Metab. 2015;100(1):E70–E76.
  • Chuanxin Z, Shengzheng W, Lei D, et al. Progress in 11β-HSD1 inhibitors for the treatment of metabolic diseases: A comprehensive guide to their chemical structure diversity in drug development. Eur J Med Chem. 2020;191:112134.
  • Markey K, Mitchell J, Botfield H, et al. 11β-hydroxysteroid dehydrogenase type 1 inhibition in idiopathic intracranial hypertension: a double-blind randomized controlled trial. Brain Commun. 2020;2(1):fcz050.
  • Mortezaee K. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and liver fibrosis: A review. Cell Biochem Funct. 2018;36(6):292–302.
  • Lee SR, An EJ, Kim J, et al. Function of NADPH oxidases in diabetic nephropathy and development of NOX inhibitors. Biomol Ther (Seoul)). 2020;28(1):25–33.
  • Hayashi M, Tojo A, Shimosawa T, et al. The role of adrenomedullin in the renal NADPH oxidase and (pro) renin in diabetic mice. J Diabetes Res. 2013;2013:1–8.
  • Sedeek M, Gutsol A, Montezano AC, et al. Renoprotective effects of a novel NOX1/4 inhibitor in a mouse model of Type 2 diabetes. Clin Sci. 2013;124(3):191–202.
  • Toulis KA, Nirantharakumar K, Pourzitaki C, et al. Glucokinase activators for type 2 diabetes: challenges and future developments. Drugs. 2020;80(5):467–475.
  • Vella A, Freeman JL, Dunn I, et al. Targeting hepatic glucokinase to treat diabetes with TTP399, a hepatoselective glucokinase activator. Sci Transl Med. 2019;11(475):eaau3441.
  • Katz L, Manamley N, Snyder WJ, et al. AMG 151 (ARRY-403), a novel glucokinase activator, decreases fasting and postprandial glycaemia in patients with type 2 diabetes. Diabetes Obes Metab. 2016;18(2):191–195.
  • Zhu X, Zhu D, Li X, et al. Dorzagliatin (HMS5552), a novel dual-acting glucokinase activator, improves glycaemic control and pancreatic β-cell function in patients with type 2 diabetes: a 28-day treatment study using biomarker-guided patient selection. Diabetes Obes Metab. 2018;20(9):2113–2120.
  • Sun C, Zhou J. Trichostatin A improves insulin stimulated glucose utilization and insulin signaling transduction through the repression of HDAC2. Biochem Pharmacol. 2008;76(1):120–127.
  • Christensen DP, Dahllöf M, Lundh M, et al. Histone deacetylase (HDAC) inhibition as a novel treatment for diabetes mellitus. Mol Med. 2011;17(5-6):378–390.
  • Larsen L, Tonnesen M, Ronn SG, et al. Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells. Diabetologia. 2007;50(4):779–789.
  • Li H, Gao Z, Zhang J, et al. Sodium butyrate stimulates expression of fibroblast growth factor 21 in liver by inhibition of histone deacetylase 3. Diabetes. 2012;61(4):797–806.
  • Makkar R, Behl T, Arora S. Role of HDAC inhibitors in diabetes mellitus. Curr Res Transl Med. 2020;68(2):45–50.
  • You Q, Chen F, Wang X, et al. Anti-diabetic activities of phenolic compounds in muscadine against alpha-glucosidase and pancreatic lipase. LWT - Food Sci Technol. 2012;46(1):164–168.
  • Lunagariya NA, Patel NK, Jagtap SC, et al. Inhibitors of pancreatic lipase: state of the art and clinical perspectives. EXCLI J. 2014;13:897.
  • Kumar P, Dubey KK. Current trends and future prospects of lipstatin: a lipase inhibitor and pro-drug for obesity. RSC Adv. 2015;5(106):86954–86966.
  • Berger M, Scheel DW, Macias H, et al. Gαi/o-coupled receptor signaling restricts pancreatic β-cell expansion. Proc Natl Acad Sci U S A. 2015;112(9):2888–2893. 2015/02/18:
  • Aaboe K, Krarup T, Madsbad S, et al. GLP-1: physiological effects and potential therapeutic applications. Diabetes Obes Metabol. 2008;10(11):994–1003.
  • Edfalk S, Steneberg P, Edlund H. Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes. 2008;57(9):2280–2287.
  • Eleazu C, Charles A, Eleazu K, et al. Free fatty acid receptor 1 as a novel therapeutic target for type 2 diabetes mellitus-current status. Chem Biol Interact. 2018;289:32–39.
  • Jeon JY, Lee H, Park J, et al. The regulation of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase by autophagy in low-glycolytic hepatocellular carcinoma cells. Biochem Biophysic Res Commun. 2015;463(3):440–446.
  • Lee YH, Wang MY, Yu XX, et al. Glucagon is the key factor in the development of diabetes. Diabetologia. 2016;59(7):1372–1375.
  • Tillner J, Posch MG, Wagner F, et al. A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo-controlled first-in-human and first-in-patient trials. Diabetes Obes Metab. 2019;21(1):120–128.
  • Scheen AJ, Paquot N, Lefèbvre PJ. Investigational glucagon receptor antagonists in Phase I and II clinical trials for diabetes. Expert Opin Investig Drugs. 2017;26(12):1373–1389.
  • Nguyen-Pham TN, Lim MS, Nguyen TAT, et al. Type I and II interferons enhance dendritic cell maturation and migration capacity by regulating CD38 and CD74 that have synergistic effects with TLR agonists. Cell Mol Immunol. 2011;8(4):341–347.
  • Dasu MR, Devaraj S, Park S, et al. Increased toll-like receptor (TLR) activation and TLR ligands in recently diagnosed type 2 diabetic subjects. Diabetes Care. 2010;33(4):861–868.
  • Singh K, Agrawal NK, Gupta SK, et al. Increased expression of endosomal members of toll-like receptor family abrogates wound healing in patients with type 2 diabetes mellitus. Int Wound J. 2016;13(5):927–935.
  • Nackiewicz D, Dan M, He W, et al. TLR2/6 and TLR4-activated macrophages contribute to islet inflammation and impair beta cell insulin gene expression via IL-1 and IL-6. Diabetologia. 2014;57(8):1645–1654.
  • Fagundes-Netto FS, Anjos PMF, Volpe CMO, et al. The production of reactive oxygen species in TLR-stimulated granulocytes is not enhanced by hyperglycemia in diabetes. Int Immunopharmacol. 2013;17(3):924–929.
  • Kopp A, Buechler C, Bala M, et al. Toll-like receptor ligands cause proinflammatory and prodiabetic activation of adipocytes via phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase but not interferon regulatory factor-3. Endocrinol. 2010;151(3):1097–1108.
  • Bajpai S, Dhayani A, Vemula PK, et al. A comprehensive role of Toll-like receptors (TLRs) in diabetic wound healing. BioRxiv. 2019.
  • Ji Y, Sun S, Shrestha N, et al. Toll-like receptors TLR2 and TLR4 block the replication of pancreatic β cells in diet-induced obesity. Nat Immunol. 2019;20(6):677–686.
  • Vennekens R, Mesuere M, Philippaert K. TRPM5 in the battle against diabetes and obesity. Acta Physiol. 2018;222(2):e12949.
  • Voets T, Vriens J, Vennekens R. Targeting TRP channels-valuable alternatives to combat Pain, lower urinary tract disorders, and type 2 Diabetes? Trends Pharmacol Sci. 2019;40(9):669–683.
  • Philippaert K, Pironet A, Mesuere M, et al. Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. Nat Commun. 2017;8(1):16.
  • Chapman NA, Duprè DJ, Rainey JK. The apelin receptor: physiology, pathology, cell signalling, and ligand modulation of a peptide-activated class A GPCR. Biochem Cell Biol. 2014;92(6):431–440. 2014/08/20:
  • O’Harte FPM, Parthsarathy V, Hogg C, et al. Long-term treatment with acylated analogues of apelin-13 amide ameliorates diabetes and improves lipid profile of high-fat fed mice. PloS One. 2018;13(8):e0202350.
  • Hu H, He L, Li L, et al. Apelin/APJ system as a therapeutic target in diabetes and its complications. Mol Genet Metab. 2016;119(1-2):20–27.
  • Soveral G, Nielsen S, Casini A. Aquaporins in health and disease: new molecular targets for drug discovery. Boca Raton, FL, USA: CRC Press, Taylor & Francis Group; 2018.
  • Méndez-Giménez L, Ezquerro S, da Silva IV, et al. Pancreatic aquaporin-7: a novel target for anti-diabetic drugs? Front Chem. 2018;6:99.
  • Borg ML, Massart J, Schönke M, et al. Modified Ucn2 peptide acts as an insulin sensitizer in skeletal muscle of obese mice. Diabetes. 2019;68(7):1403–1414.
  • Dun XP, Parkinson DB. Role of netrin-1 signaling in nerve regeneration. IJMS. 2017;18(3):491.
  • Gao S, Zhang X, Qin Y, et al. Dual actions of Netrin-1 on islet insulin secretion and immune modulation. Clin Sci (Lond)). 2016;130(21):1901–1911.
  • Yimer EM, Zewdie KA, Hishe HZ. Netrin as a novel biomarker and its therapeutic implications in diabetes mellitus and diabetes-associated complications. J Diabetes Res. 2018;2018:8250521.
  • Liu C, Qinan W, XiaoTian L, et al. TERT and Akt are involved in the Par-4-dependent apoptosis of Islet β-cells in type 2 diabetes. J Diabetes Res. 2018;2018:1–13.
  • Matzinger M, Fischhuber K, Heiss EH. Activation of Nrf2 signaling by natural products-can it alleviate diabetes? Biotechnol Adv. 2018;36(6):1738–1767.
  • Zhao J, Liu L, Li X, et al. Neuroprotective effects of an Nrf2 agonist on high glucose-induced damage in HT22 cells. Biol Res. 2019;52(1):11.
  • Muse ED, Feldman DI, Blaha MJ, et al. The association of resistin with cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2015;239(1):101–108.
  • Steppan CM, Wang J, Whiteman EL, et al. Activation of SOCS-3 by resistin. Mol Cell Biol. 2005;25(4):1569–1575.
  • Lee S, Lee HC, Kwon YW, et al. Adenylyl cyclase-associated protein 1 is a receptor for human resistin and mediates inflammatory actions of human monocytes. Cell Metabol. 2014;19(3):484–497.
  • Khalil O, Alnahal A, Ghonium M, et al. Does resistin gene polymorphisms +299 (G > A) participate in insulin resistance in Egyption non-obese type 2 diabetes? Int J Genomic Med. 2014;2:1.
  • Fawzy F, Osama K, Salem H, et al. Resistin gene polymorphism in offspring of patients with type 2 diabetes mellitus. Paper presented at: 18th European Congress of Endocrinology; Munich, Germany, 2016.
  • Chhipa AS, Borse SP, Baksi R, et al. Targeting receptors of advanced glycation end products (RAGE): preventing diabetes induced cancer and diabetic complications. Pathol Res Pract. 2019;215(11):152643.
  • Zheng H, Wu J, Jin Z, et al. Protein modifications as manifestations of hyperglycemic glucotoxicity in diabetes and its complications. Biochem Insights. 2016;9:1–9.
  • Rudman N, Gornik O, Lauc G. Altered N-glycosylation profiles as potential biomarkers and drug targets in diabetes. FEBS Lett. 2019;593(13):1598–1615.
  • Halestrap AP. The SLC16 gene family structure, role and regulation in health and disease. Mol Aspects Med. 2013;34(2-3):337–349.
  • Stadler LK, Farooqi IS. A new drug target for type 2 diabetes. Cell. 2017;170(1):12–14.
  • Gurfinkel R, Joy TR. Anacetrapib: Hope for CETP Inhibitors? Cardiovasc Ther. 2011;29(5):327–339.
  • Masson W, Lobo M, Siniawski D, et al. Therapy with cholesteryl ester transfer protein (CETP) inhibitors and diabetes risk. Diabetes Metabol. 2018;44(6):508–513.
  • Barter PJ, Cochran BJ, Rye KA. CETP inhibition, statins and diabetes. Atherosclerosis. 2018;278:143–146.
  • Mirzaei H, Masoudifar A, Sahebkar A, et al. MicroRNA: a novel target of curcumin in cancer therapy. J Cell Physiol. 2018;233(4):3004–3015.
  • Pordzik J, Jakubik D, Jarosz-Popek J, et al. Significance of circulating microRNAs in diabetes mellitus type 2 and platelet reactivity: bioinformatic analysis and review. Cardiovasc Diabetol. 2019;18(1):113.
  • LaPierre MP, Stoffel M. MicroRNAs as stress regulators in pancreatic beta cells and diabetes. Mol Metabol. 2017;6(9):1010–1023.
  • Kokkinopoulou I, Maratou E, Mitrou P, et al. Decreased expression of microRNAs targeting type-2 diabetes susceptibility genes in peripheral blood of patients and predisposed individuals. Endocrine. 2019;66(2):226–239.
  • Hezova R, Slaby O, Faltejskova P, et al. microRNA-342, microRNA-191 and microRNA-510 are differentially expressed in T regulatory cells of type 1 diabetic patients. Cell Immunol. 2010;260(2):70–74.
  • Ying C, Sui-Xin L, Kang-Ling X, et al. MicroRNA-492 reverses high glucose-induced insulin resistance in HUVEC cells through targeting resistin. Mol Cell Biochem. 2014;391(1-2):117–125.
  • Khunti S, Davies MJ, Khunti K. Clinical inertia in the management of type 2 diabetes mellitus: a focused literature review. Br J Diabetes. 2015;15(2):65–69.
  • Boccardi V, Murasecco I, Mecocci P. Diabetes drugs in the fight against Alzheimer's disease. Ageing Res Rev. 2019; 54:100936.
  • Goodarzi MO, Rotter JI. Genetics insights in the relationship between type 2 diabetes and coronary heart disease. Circ Res. 2020;126(11):1526–1548.
  • Zafar S, Sachdeva M, Frankfort BJ, et al. Retinal neurodegeneration as an early manifestation of diabetic eye disease and potential neuroprotective therapies. Curr Diab Rep. 2019;19(4):17.
  • Muskiet MH, Wheeler DC, Heerspink HJ. New pharmacological strategies for protecting kidney function in type 2 diabetes. Lancet Diabetes Endocrinol. 2019;7(5):7:397–412. (18)30263-8
  • Hobabagabo AF, Sumner AE. Forced migration and foot care in people with diabetes. Lancet Diabetes Endocrinol. 2020;8(2):100.
  • CenterWatch [Internet]. Washington (DC): Thomson CenterWatch; [cited 2019. Nov 8]. Available from: https://www.centerwatch.com/directories/1067-fda-approved-drugs.
  • Saeedi P, Salpea P, Karuranga S, et al. Mortality attributable to diabetes in 20–79 years old adults, 2019 estimates. Diabetes Res Clin Pract. 2020;162:108086.
  • Anderson SL, Beutel TR, Jennifer M. Oral semaglutide in type 2 diabetes. J Diabetes Complications. 2020;34(4):107520.
  • Artasensi A, Pedretti A, Vistoli G, et al. Type 2 diabetes mellitus: a review of multi-target drugs. Molecules. 2020;25(8):1987.
  • Grunberger G. Should side effects influence the selection of antidiabetic therapies in type 2 diabetes? Curr Diab Rep. 2017;17(4):21.
  • Cheng AY. So many anti-hyperglycemics: how to choose? a practical approach. Can J Diabetes. 2017;41(5):469–473.
  • Lu K, Su B, Meng X. Recent advances in the development of vaccines for diabetes, hypertension, and atherosclerosis. J Diabetes Res. 2018;2018:1638462.
  • Peng BY, Dubey NK, Mishra VK, et al. Addressing stem cell therapeutic approaches in pathobiology of diabetes and its complications. J Diabetes Res. 2018;2018:7806435.
  • Florez JC. Mining the genome for therapeutic targets. Diabetes. 2017;66(7):1770–1778.
  • Zeng Z, Huang S, Sun T. Pharmacogenomic studies of current antidiabetic agents and potential new drug targets for precision medicine of diabetes. Diabetes Ther. 2020;11(11):2521–2538.
  • Li Y, Xu K, Xu K, et al. Roles of identified long noncoding RNA in diabetic nephropathy. J Diabetes Res. 2019;2019:1–8.
  • Wollam J, Riopel M, Xu YJ, et al. Microbiota-produced N-formyl peptide fMLF promotes obesity-induced glucose intolerance. Diabetes. 2019;68(7):1415–1426.
  • Tiwari N, Thakur AK, Kumar V, et al. Therapeutic targets for diabetes mellitus: an update. Clin Pharmacol Biopharm. 2014;3:117.
  • Kahn S, Hull R, Utzschneider K. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840–846.
  • Ni Y, Ni L, Zhuge F, et al. Adipose tissue macrophage phenotypes and characteristics: the key to insulin resistance in obesity and metabolic disorders. Obesity (Silver Spring). 2020;28(2):225–234.
  • Yacir B, Mohammed T. Molecular mechanisms underlying obesity-induced hypothalamic inflammation and insulin resistance: pivotal role of resistin/TLR4 pathways. Front Endocrinol. 2019;10:140.
  • Sabry MM, Dawood AF, Rashed LA, et al. Relation between resistin, PPAR-γ, obesity and atherosclerosis in male albino rats. Arch Physiol Biochem. 2019;126(5):389–398.
  • Aamir K, Khan HU, Sethi G, et al. Wnt signaling mediates TLR pathway and promote unrestrained adipogenesis and metaflammation: Therapeutic targets for obesity and type 2 diabetes. Pharmacol Res. 2020;152:104602.
  • Nolen-Doerr E, Stockman M, Rizo I. Mechanism of glucagon-like peptide 1 improvements in type 2 diabetes mellitus and obesity. Curr Obes Rep. 2019;8(3):284–291.
  • Kai-Zhen S, Yan-Run L, Di Z, et al. Relation of circulating resistin to insulin resistance in type 2 diabetes and obesity: a systematic review and meta-analysis. Front Physiol. 2019;10:1399.
  • Zsombok A, Derbenev AV. TRP channels as therapeutic targets in diabetes and obesity. Pharmaceuticals. 2016;9(3):50.
  • Newman DJ, Cragg GM. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod. 2020;83(3):770–803. −
  • Prabhakar P, Banerjee M. Antidiabetic phytochemicals: a comprehensive review on opportunities and challenges in targeted therapy for herbal drug development. Int J Pharm Res. 2020;12:1673–1696.
  • Mohanta D, Ghangal R, Solank M, et al. Delivery of microbial metabolites for human health care: a review. Environ Chem Lett. 2020;18(3):595–603.
  • Lauritano C, Ianora A. Marine organisms with anti-diabetes properties. Mar Drugs. 2016;14(12):220.
  • Wang Y, Liu L, Wang YS, et al. Actinoplanes utahensis ZJB-08196 fed-batch fermentation at elevated osmolality for enhancing acarbose production. Bioresour Technol. 2012;103(1):337–342.
  • Yoon S, Lee SR, Hwang Y, et al. Fridamycin A, a microbial natural product, stimulates glucose uptake without inducing adipogenesis. Nutrients. 2019;11(4):765.

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