Dynamics of total volume of pancreatic α‐ and β ‐cells under the influence sulfonylureas and their combination with dipeptidyl peptidase‐4 inhibitors

OBJECTIVE: Sulfonylureas and dipeptidyl peptidase‐4 inhibitors have a multidirectional effect on pancreatic cells. We aimed to evaluate the effects of these drugs on β‐ and α‐cells in rats aged 12 months with type 2 diabetes mellitus when administered in combination with various sulfonylureas. METHODS: Streptozotocin‐nicotinamide induced type 2 diabetes mellitus was induced in rats aged 12 months. Animals received the sulfonylureas gliclazide or glibenclamide for 24 weeks alone or in combination with the dipeptidyl peptidase‐4 inhibitor vildagliptin or vildagliptin monotherapy. Blood glucose and animal weights were measured before and during the experiment. The oral glucose tolerance test was conducted before therapy initiation. Immunohistochemical analyses were conducted after the end of the experiment using glucagon and insulin antibodies. The total volumes of α and β cells were estimated in relation to the volume of the pancreatic islets. RESULTS: The total volumes of β‐cells did not differ between the sulfonylurea group and the untreated type 2 diabetes mellitus group. The addition of dipeptidyl peptidase‐4 inhibitors to sulfonylureas normalized the total volumes of β cells. The total volumes of α‐cells in the gliclazide group and combination of gliclazide with dipeptidyl peptidase‐4 inhibitor was comparable to that in the control group of intact animals, in contrast with the glibenclamide group. CONCLUSION: The combination of vildagliptin to both sulfonylureas contributed to the normalisation of β‐cells number. Normalisation of the total volumes of α‐cells was observed with gliclazide therapy and combination of gliclazide with dipeptidyl peptidase‐4 inhibitor.