Endocrine Abstracts

Introduction: New medicinal products that have been introduced into first-line therapy for type 2 diabetes mellitus (T2DM) include glucagon-like peptide-1 receptor agonists (GLP-1ra) and dipeptidyl peptidase-4 inhibitors (DPP-4i). These products have been shown to increase beta-cell proliferation. Some studies also demonstrated an increase in pancreatic alpha-cell proliferation. Various sulfonylureas drugs (SU) have been shown to produce different effects on apoptosis pancreatic cells. Therefore, we are interested in evaluating the effects of treatment with combinations of incretin mimetics with SU on pancreatic cells.

Goal of the study: The goal of this study was to evaluate the effects of long-term therapy with combinations of incretin mimetics and SU on the ratio of alpha- and beta-cells in a model of type 2 diabetes in 12-month-old rats.

Materials and methods: Streptozotocin-nicotinamide-induced model of type 2 diabetes was used. The animals received treatment according to the assigned groups over a period of 24 months. Treatment groups (5 animals per group): 1) control group (healthy animals); 2) animals with T2DM without any treatment; 3) animals with T2DM treated with Exenatide; 4) Vildagliptin; 5) Exanatide+ Gliclazide; 6) Vildagliptin+ Gliclazide; 7) Exenatide + Glibenclamide; 8)Vildagliptin + Glibenclamide. After the end of treatment, immunohistochemistry using anti-glucagon and anti-insulin antibodies was carried out.

Results: A volume ratio of alpha- and beta-cells of the pancreas was determined relative to the area of the pancreatic islets. The volumes of beta cells in the healthy control group was comparable to those in the groups receiving monotherapy with Exenatide,Vildagliptin, their combination with SU. There were statistically significant differences in the volumes of alpha-cells in the groups receiving Glibenclamide monotherapy andin combination with GLP1ra or DPP4iin comparison with the healthy control.

Conclusions: 24-week treatment with GLP1ra and DPP4i resulted in normalization of both beta and alpha cell contents. The normalization of the content of alpha-cells in animals treated with Gliclazide-containing combinations was comparable to that observed in the groups receiving monotherapy with GLP1ra, DPP4i, and the healthy control group while the number of alpha-cells in the groups receiving incretin mimetics in combination with Glibenclamide was similar to the content of these cells observed in the group with untreated T2DM.