Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC21410.15690/vramn.v68i2.548ENDOCRINOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ЭНДОКРИНОЛОГИИFUNDAMENTAL BASES OF SEARCH OF MEDICINES FOR THERAPY OF A DIABETES MELLITUS TYPE 2ФУНДАМЕНТАЛЬНЫЕ ОСНОВЫ ПОИСКА ЛЕКАРСТВЕННЫХ СРЕДСТВ ДЛЯ ТЕРАПИИ САХАРНОГО ДИАБЕТА 2-ГО ТИПАSpasovA. A.СпасовА. А.
Russian Federation

PhD, Professor, RAMS academician, Honored Worker of Science of Russian Federationa, Head of Department for Pharmacology, Volgograd State Medical University. Address: 400131, Volgograd, Pavshikh Bortsov Sq., 1; tel.: (8442) 94-24-23

aspasov@mail.ruPetrovV. I.ПетровВ. И.
Russian Federation

PhD, Professor, RAMS academician, Honored Worker of Science of Russian Federation, Honored Doctor of Russian Federation, Chancellor of Volgograd State Medical University Address: 400131, Volgograd, Pavshikh Bortsov Sq., 1; tel.: (8442) 55-17-70

post@volgmed.ruCheplyaevaN. I.ЧепляеваН. И.
Russian Federation

Junior Research Worker, Laboratory of Antioxidants Pharmacology, Research Institute of Pharmacology, Volgograd State Medical University Address: 400131, Volgograd, Pavshikh Bortsov Sq., 1; tel.: (8442) 97-15-34

natalja-chepljaeva@rambler.ruLenskayaK. V.ЛенскаяК. В.
Russian Federation

PhD, Doctoral Student of Pharmacology Department, Volgograd State Medical University Address: 400131, Volgograd, Pavshikh Bortsov Sq., 1; tel.: (8442) 97-15-34

kina81@mail.ruVolgograd State Medical University, Russian FederationВолгоградский государственный медицинский университет, Российская Федерация22022013682Vestnik Rossiiskoi akademii medetsinskikh nauk / Annals of the Russian academy of medical sciencesВестник Российской академии медицинских наук434907082015Copyright ©; 1970, "Paediatrician" Publishers LLCCopyright ©; 1970, Издательство "Педиатръ"1970"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/214

In the presented review the data on searching for new drugs for diabetes mellitus treatment are analyzed. These drugs are used for metabolic disorder correction leading to hyperglycemia: β-cells dysfunction, peripheral insulin resistance, increased hepatic glucose output.

В обзоре проанализированы литературные данные о поиске новых препаратов для лечения сахарного диабета, направленных на коррекцию трех основных метаболических нарушений, приводящих к гипергликемии: дисфункции β-клеток, периферической инсулинорезистентности, избыточной продукции глюкозы печенью.

diabetes mellitusantidiabetic agentsсахарный диабетантидиабетические препараты1. Dedov I.I., Shestakova M.V., Suncov Ju.I. et al. Pharmacoeconomic modeling of long-term results of treatment of type 2 diabetes in patients treated with modern analogues of insulin therapy compared with oral antidiabetes drugs. Saharnyi diabet = Diabetes. 2010; 46 (1): 102–112.2. Balabolkin M.I., Klebanova E.M., Kreminskaya V.M. Treatment of diabetes and its complications. Moscow, 2005.3. Ametov A.S. The role of β-cells in the regulation of glucose homeostasis in normal and type 2 diabetes. Saharnyi diabet = Diabetes. 2008; 41 (4): 6–12.4. Stolar M.W., Hoogwerf B.J., Gorshow S.M. et al. Managing Type 2 Diabetes: Going Beyond Glycemic Control. J. Manag. Care Pharm. 2008; 14 (5): 2–19.5. Lerario A.C., Chacra A.R., Pimazoni-Netto A. et al. Algorithm for the treatment of type 2 diabetes: a position statement of Brazilian Diabetes Society. Diabetology& Metabolic Syndrome. 2010; 35 (2).6. Dedov I.I., Shestakova M.V. Algorithms for specialized medical care to patients with diabetes mellitus. Moscow, 2007.7. Spasov A.A., Chepurnova M.V. Scientific approaches to the combined treatment of diabetes type 2. Vestnik VolgGMU = Bulletin of Volgograd State Medical University. 2011; 1: 8–12.8. Saharnyi diabet: diagnostika, lechenie, profilaktika. Pod red. I.I. Dedova, M.V. Shestakovoi [Diabetis: Diagnosis. Treatment, Prophylaxis. Edited by I.I. Dedov, M.V. Shestakova]. Moscow, MIA, 2011. 808 p.9. O’Moore-Sullivan T.M., Prins J.B. Thiazolidinediones and type 2 diabetes: new drugs for an old disease. MJA. 2002; 116: 381–386.10. Graham D.J., Ouellet-Hellstrom R., MaCurdy T.E. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly medicare patients treated with rosiglitazone or pioglitazone. JAMA. 2010; 304 (4): 411–418.11. Levien, T.L., Baker DE. New drugs in development for the treatment of diabetes. Diabetes Spectrum. 2009; 22: 92–106.12. Sharma R. Novel dual-acting peroxisome proliferator-activated receptor alpha and gamma agonists. J. Clin. Diagn. Res. 2008; 2: 659–667.13. Johnson T.O., Ermolieff J., Jirousek M.R. Protein tyrosine phosphatase 1b inhibitors for diabetes. Drug discovery. 2002; 1: 696–709.14. Ukkola O., Santaniemi M. Protein tyrosine phosphatase 1B: a new target for the treatment of obesity and associated co-morbidities. J. Intern. Med. 2002; 251: 467–475.15. Kumar Vats R., Kumar V., Kothari A. et al. Emerging targets for diabetes. Curr. sci. 2005; 88 (2): 241–249.16. Black E., Breed J., Breeze A. L. et al. Structure-based design of protein tyrosine phosphatase-1B inhibitors. Bioorg. & Medicinal Chem. 2005; 15: 2503–2507.17. Wilson D.P., Wan Z.K., Xu W.X. et al. Structure-based optimization of protein tyrosine phosphatase 1B inhibitors: from the active site to the second phosphotyrosine binding site. J. Med. Chem. 2007; 50: 4681–4698.18. Coman O.A., Paunescu H., Ghita I. et al. Beta 3 adrenergic receptors: molecular, histological, functional and pharmacological approaches. Romanian J. Morphol. Embryol. 2009; 50 (2): 169–179.19. Schaeffer P., Bernat A., Arnone M. et al. Effect of SR58611A, a potent beta-3 adrenoceptor agonist, on cutaneous wound healing in diabetic and obese mice. Eur. J. Pharmacol. 2006; 529 (1–3): 172–178.20. Francke S. TAK-677 (Dainippon/Takeda). Curr. Opin. Investig. Drug. 2002; 11 (3): 1624–1628.21. Sakurai H.A New concept: the use of vanadium complexes in the treatment of diabetes mellitus. Chem. Rec. 2002; 2: 237–248.22. Thompson K.H., Lichter J., Le Be C. Vanadium treatment of type 2 diabetes: A view to the future. J. Inorganic Biochem. 2009; 103: 554–558.23. Gallwitz B. The evolving place of incretin-based therapies in type 2 diabetes. Pediatr. Nephrol. 2010; 25: 1207–1217.24. Ranganath L.R. The entero-insular axis: implications for human metabolism. Clin. Chem. Lab. Med. 2008; 46 (1): 43–56.25. Ross A.S. Incretin agents in type 2 diabetes. Can. Fam. Physician. 2010; 56: 639–648.26. Dharmalingam M., Sriram U., Baruah M.P. Liraglutide: A review of its therapeutic use as a once daily GLP-1 analog for the management of type 2 diabetes mellitus. Indian J. Endocrinol. Metab. 2011; 15 (1): 9–17.27. Chena D., Liaoa J., Lia N. et al. A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db/ db mice. PNAS. 2007; 104 (3): 943–948.28. Gorrell M.D. Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders. Clin. Sci. 2005; 108: 277–292.29. Gupta R, Walunj S.S., Tokala R.K. Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of type 2 diabetes. Curr. Drug Targets. 2009; 10: 71–87.30. Green B.D., Flatt P.R. Incretin hormone mimetics and analogues in diabetes therapeutics. Best Pract. Res. Clin. Endocrinol. Metab. 2007; 4 (21): 497–516.31. Overton H.A., Fyfe M.C.T., Reynet C. GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity. Brit. J. Pharmacol. 2008; 153: 76–81.32. Spasov A.A., Bulanov A.E., Samohina M.P. Antidiabetic properties of Gymnema sylvestre (review). Himiko-farmacevticheskij zhurnal = Chemistry and pharmaceutical journal. 2008; 42 (11): 10–14.33. Fushiki T., Kojima A., Imoto T. An extract of Gymnema sylvestre leaves and purified gymnemic acid inhibits glucose-stimulated gastric inhibitory peptide secretion in rats. J. Nutr. 1992; 122: 2367–2373.34. Matschinsky F.M. Assessing the potential of glucokinase activators in diabetes therapy. Nat. Rev. Drug Disc. 2009; 8: 399–416.35. Matschinsky F.M., Porte D. Glucokinase activators (GKAs) promise a new pharmacotherapy for diabetics. F1000. Med. Reports. 2010; 43 (2): 1776–1783.36. Spasov A.A., Petrov V.I., Anisimova V.A. et al. Materialy IV Vserossiiskogo diabetologicheskogo kongressa [Proceedings of 4th Russian National Diabetic Congress]. Moscow, 2008. 336 p.37. Fujimoto K., Polonsky K. S. Pdx1 and other factors that regulate pancreatic в-cell survival. Diabetes Obes. Metab. 2009; 11 (Suppl. 4.): 30–37.38. Robertson R.P., Harmon J.S. Pancreatic islet β-cell and oxidative stress: the importance of glutathione peroxidase. FEBS Lett. 2007; 581 (19): 3743–3748.39. Poltorak V.V., Gorbenko N.I., Sakalo E.A. Prevention of type 1 diabetes mellitus: pathophysiological rationale,40. strategy and clinical implementation. Ukrainskii medicinskiij chasopis = Ukranian medical bulletin. 2001; 22 (2): 83–91.41. Yonemura, Y., Takashima T., Miwa K. et al. Amelioration of diabetes mellitus in partially depancreatized rats by poly(ADP-ribose) synthetase inhibitors: evidence of islet B-cell regeneration. Diabetes. 1984; 33: 401–404.42. Sandler S., Andersson A. Stimulation of cell replication in transplanted pancreatic islets by nicotinamide treatment. Transplantation. 1988; 46: 30–31.43. Manna R., Migliore A., Martin L.S. et al. Nicotinamide treatment in subjects at high risk of developing IDDM improves insulin secretion. Brit. J. Clin. Pract. 1992; 46: 177–179.44. Hu Y., Wang Y., Wang L. et al. Effects of nicotinamide on prevention and treatment of streptozotocin-induced diabetes mellitus in rats. Chin. Med. J. (Engl.). 1996; 109 (11): 819–822.45. Pozzilli P., Visalli N., Cavallo M.G. Vitamin E and nicotinamide have similar effects in maintaining residual beta cell function in recent onset insulin-dependent diabetes (the IMDIAB IV study). Eur. J. Endocrinol. 1997; 137: 234–239.46. Crino A., Schiaffini R., Manfrini S. A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX). Eur. J. Endocrinol. 2004; 150: 719–724.47. Zhou S.-S., Li D., Sun W.-P. Nicotinamide overload may play a role in the development of type 2 diabetes. World J. Gastroenterol. 2009; 43 (15): 5674–5684.48. Jagtap P. G., Baloglu E., Southan G. J. et al. Discovery of potent poly(ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone. J. Med. Chem. 2005; 48: 5100–5103.49. Szabo C., Biser A., Benko R. et al. Poly(ADP-Ribose) polymerase inhibitors ameliorate nephropathy of type 2 diabetic Leprdb/db mice. Diabetes. 2006; 55 (11): 3004–3012.50. Pittenger G.L., Taylor-Fishwick D., Vinik A.I. The role of islet neogeneis-associated protein (INGAP) in pancreatic islet neogenesis. Curr. Protein Pept Sci. 2009; 10 (1): 37–45.51. Dungan K.M., Buse J.B., Ratner R.E. Effects of therapy in type 1 and type 2 diabetes mellitus with a peptide derived from islet neogenesis associated protein (INGAP). Diabetes Metab. Res. Rev. 2009; 25 (6): 558–565.52. Bottino R., Balamurugan A.N., Tse H. Response of human islets to isolation stress and the effect of antioxidant treatment. Diabetes. 2004; 53: 2559–2568.53. Felig P., Wahren J. Influence of endogenous insulin secretion on splanchnic glucose and amino acid metabolism in man. J. Clin. Invest. 1971; 50 (8): 1702–1711.54. Wu C., Okar D. A., Kang J. et al. Reduction of hepatic glucose production as a therapeutic target in the treatment of diabetes. Curr. Drug Targets Immune, Endocrine & Metab. Dis. 2005; 5: 51–59.55. Alice Y.Y., Cheng I., Fantus G. Oral antihyperglycemic therapy for type 2 diabetes mellitus. CMAJ. 2005; 172 (2): 213–226.56. Long Y.C., Zierath J.R. AMP-activated protein kinase signaling in metabolic regulation. J. Clin. Invest. 2006; 116: 1776–1783.57. Meijer L., Flajolet M., Greengard P. Pharmacological inhibitors of glycogen synthase kinase 3. Trends in Pharmacol. Sci. 2004; 25 (9): 471–480.58. Woodgett J.R. Physiological roles of glycogen synthase kinase-3: potential as a therapeutic target for diabetes and other disorders. Curr. Drug Targets Immune, Endocrine & Metab. Dis. 2003; 3: 275–284.59. Bergans N., Stalmans W., Goldmann S. et al. Molecular mode of inhibition of glycogenolysis in rat liver by the dihydropyridine derivative, BAY R3401: inhibition and inactivation of glycogen phosphorylase by an activated metabolite. Diabetes. 2000; 49(9): 1419–1426.60. Martin W.H., Hoover D.J., Armento S.J. et al. Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. PNAS. 1998; 95 (4): 1776–1781.61. Herling A.W., Burger H.-J., Schwab D. Pharmacodynamic profile of a novel inhibitor of the hepatic glucose-6-phosphatase system. Am. J. Physiol. 1998; 274: 1087–1093.62. Gallagher M.P., Goland R.S., Greenbaum C.J. Making progress: preserving beta cells in type 1 diabetes. Ann. N.-Y. Acad. Sci. 2011; 1243: 119–134.63. Bhaskar V., Goldfine I.D., Bedinger D.H. et al. A fully human, allosteric monoclonal antibody that activates the insulin receptor and improves glycemic control. Diabetes. 2012; 61 (5): 1263–1271.64. Petrov V.I., Rogova N.V., Ryazanova A.Ju. et al. Ultra-low doses of antibodies to the C-terminal fragment of β-subunit of the insulin receptor - a new class of antidiabetic agents. Byulleten' VNC RAMN = Bulletin of RAMS Volgograd RI. 2009; 3: 19–22.65. Gu W., Yan H., Winters K. A. et al. Long-term inhibition of the glucagon receptor with a monoclonal antibody in mice causes sustained improvement in glycemic control, with reversible β-cell hyperplasia and hyperglucagonemia. J. Pharmacol. Exp. Therapeutics. 2009; 331 (3): 871–881.66. Jabbour S.A. The importance of reducing hyperglycemia while preserving insulin secretion — the rationale for sodium-coupled glucose co-transporter 2 inhibition in diabete. US Endocrinol. 2009; 5: 75–78.67. Norton L., De Fronzo R.A., Abdul-Ghani M.A. Sodium-glucose co-transporter 2 inhibition — a novel strategy for glucose control in type 2 diabetes. US Endocrinol. 2010; 6: 42–47.68. Chao E.C., Henry R.R. SGLT2 inhibition — a novel strategy for diabetes treatment. Nat. Rev. Drug Discov. 2010; 9 (7): 551–559.