Open AccessComparing hypoglycemic activity of novel GPR119 agonist and DPP-4 inhibitor sitagliptin
Author(s) -
I. N. Tyurenkov,
Тюренков Иван Николаевич,
Д. В. Куркин,
Куркин Денис Владимирович,
Д. А. Бакулин,
Бакулин Дмитрий Александрович,
Е. В. Волотова,
Волотова Елена Владимировна,
Mikhail Chafeev,
Шафеев Михаил Айратович
Publication year - 2016
Publication title -
problemy èndokrinologii
Language(s) - English
Resource type - Journals
eISSN - 2308-1430
pISSN - 0375-9660
DOI - 10.14341/probl201662138-43
Subject(s) - sitagliptin , medicine , endocrinology , postprandial , dipeptidyl peptidase 4 , hypoglycemia , agonist , incretin , type 2 diabetes , diabetes mellitus , streptozotocin , receptor , chemistry
Hypoglycemic drugs affecting the incretin system increasingly becoming popular because of its high safety and efficacy. The regulation of the secretion of endogenous incretin involves a number of receptors on the enteroendocrine cells, among which the most promising is GPR119. After activation it increases the incretins secretion and glucose-dependent insulin secretion, that is important from the point of view of effective control of postprandial glucose levels with minimal risk of hypoglycemia.Aims.To conduct a comparative study of hypoglycemic activity of DPP-4 inhibitors (sitagliptin) and novel GPR119 agonist receptor — compound ZB-16 in streptozotocin-nicotinamide-induced rat model of type 2 diabetes mellitus (T2DM).Material and methods.The hypoglycemic effect of ZB-16 (0.1 and 1 mg/kg per os) and sitagliptin (10 mg/kg per os) was studied during 4-week administration in 50 adult female rats (6 months, 240—260 g) with streptozotocin-nicotinamide-induced T2DM. The oral glucose tolerance test (OGTT) was performed on the 14th and 28th day after the start of treatment.Results.Animals receiving compound ZB-16 at a dose of 1 mg/kg by the end of treatment there have a significant reduction in fasting glucose as compared with the control group (7.9±0.43 and 0.54±9,6 mmol/l, respectively). During the OGTT on day 28 of treatment compound ZB-16 improves the rate of glucose utilization, reducing «peak» of growth glycemia (15,7±0,88 versus 21,6±1,06 mmol/L) and area under the curve «glucose concentration-time» (to 25%) compared with the control group during the OGTT.Conclusions.Novel GPR119 agonist — ZB-16 (1 mg/kg) has a clear hypoglycemic effect comparable to that of sitagliptin in rats with streptozotocin-nicotinamide-induced T2DM.