Cyclic-imide derivative (5e) attenuates hyperglycemia in type 1 diabetic rats by protecting pancreatic cells and enhancing insulin secretion

Diabetes is a major cause of cardiovascular complications, accounting for nearly 70% of diabetes-related deaths. In a previous study, several novel cyclic-imide compounds were evaluated as hypoglycemic agents, and one compound, 5e, showed promising effects in controlling blood glucose in a type 1 diabetes (T1D) rat model. The purpose of this investigation was to clarify the processes by which 5e reduces hyperglycemia through tolerance tests, metabolic hormone assessment, and evaluation of anti-apoptotic effects on pancreatic tissue. Forty male Sprague-Dawley rats allocated to five categories: control, diabetic, diabetic administered glibenclamide (10 mg/kg), and diabetic treated with 5e at two doses (10 and 15 mg/kg). Over two weeks, blood glucose and tolerance tests were performed, and on day 15, blood and pancreatic tissues were collected for analysis of insulin, glucagon, lipase, and amylase, along with histological evaluation. Both 5e and glibenclamide reduced blood glucose by approximately 36%, while the higher dose of 5e lowered glycemia by 50%. All treated groups showed improved glycemic control in tolerance tests, with the 15 mg/kg 5e group demonstrating the greatest glucose clearance and insulin sensitivity. Compound 5e modulated insulin, glucagon, and lipase levels, indicating metabolic improvement, with the strongest effects at the higher dose. Histological analysis revealed enhanced islet morphology and significantly reduced pancreatic apoptosis, particularly in the higher dose 5e group. These findings suggest that 5e improves glycemic control and exerts protective effects on pancreatic structure and function in T1D rats, highlighting its potential as a therapeutic agent and warranting further pharmacological investigation.