Effects of saxagliptin and sitagliptin on glycaemic control and pancreatic ß-cell mass in a streptozotocin-induced mouse model of type 2 diabetes.

ABSTRACT

AIMS: We examined the effects of the oral dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin on glycaemic control and pancreatic ß-cell mass and morphology in a mouse model of type 2 diabetes mellitus (T2DM). METHODS: Male C57BL/6 mice (n = 12/group) aged 4 to 6 weeks and weighing >15 g received a high-fat diet throughout this 45-day study. After a 7-day handling period, baseline levels of plasma glucose, plasma insulin and glycated haemoglobin (HbA1c) were assessed. Animals were allocated to one of six groups compound vehicle control, intraperitoneal streptozotocin (STZ, 50 mg/kg)-treated control and saxagliptin (10 mg/kg) or sitagliptin (10 mg/kg, positive control) initiated 7 days before or 1 day after STZ administration. Endpoints included changes in body weight, food and water consumption, glucose tolerance (approximately 3 weeks post-STZ), fasting glucose and HbA1c and immunohistochemical analyses of the pancreas. RESULTS: Body weight, weight gain and food intake were reduced in STZ versus control mice. DPP-4 inhibitor treatment did not affect these changes, but the increase in water intake observed post-STZ administration was significantly attenuated with DPP-4 inhibitors whether initiated before or after STZ injury. Small but significant improvements in glycaemic control were observed with DPP-4 inhibitors versus the STZ control. Improved ß-cell mass and morphology were observed with saxagliptin given pre- or post-STZ and sitagliptin given post-STZ. CONCLUSIONS: Saxagliptin mitigated damage to ß-cells and improved glycaemic control in this mouse model of T2DM.