Effect and mechanism of action of Sulfonylthiourea derivative on glycemia homeostasis

Introduction: Sulfonylureas, are used worldwide as insulin secretagogues in the treatment of diabetes. In this sense, glibenclamide, a 2nd generation sulfonylurea, was chemically modified with the intention of investigating its effect on glucose homeostasis. Aim: To assess the glycemic, insulin and GLP-1 levels of a glibenclamide derivative sulphonylthyourea 7 (Sulph7) in the glucose tolerance test (TTG). Next, evaluate whether this derivative secretes insulin in vitro and acts on the intestinal disaccharidases. Methods: Male Wistar rats (50 days old) were divided into three experimental groups: Group I, Hyperglycemic rats (4g/kg glucose, via oral (v.o)), Group II, Hyperglycemic rats plus Glibenclamide (10 mg/kg, v.o., 30 min before glucose overload), and Group III, Hyperglycemic rats plus Sulph7 (10 mg/kg, v.o., 30 min before glucose overload). Sitagliptin (10 mg/kg, v.o., 1 h before glucose overload) was administered to analyze GLP-1 levels. Blood samples were collected prior to glucose overload (time 0); and 15, 30, 60 and 180 min after, to quantify glucose, insulin and GLP-1 levels. At 180 min the animals were euthanized and gut samples were taken to analyze the activity of the disaccharidases. Pancreatic islets were isolated to quantify insulin in vitro. Results expressed as Mean ± Standard Error Mean and level of significance of 95% (p <0.05), (CEUA protocol approved: PP00749). Results: Sulph 7 reduced blood glucose and increased insulin and GLP-1 levels in GTT. Sulph 7 also increased insulin levels, in vitro, and decreased the activities of intestinal disaccharidases. Conclusions: Suph 7 lowers blood glucose by acting on three glucose homeostasis targets: by increasing insulin and GLP-1 secretion and by reducing intestinal disaccharidases.