Morphological features of pancreatic endocrinicytes in rats with type 2 diabetes mellitus receiving the incretin mimetic therapy of different duration

Abstract

Drugs based on incretin effects, including analogs of glucagon-like peptide-1 (GLP1) and dipeptidyl peptidase-4 inhibitors (DPP4), increase replication and inhibit apoptosis of β-cells. Incretin mimetics can influence the function of α-cells thereby restoring physiological regulation of glucagon. However, effects of incretin mimetics on proliferation and apoptosis of α-cells are understudied. A few studies reported increased α-cell proliferation, but the factors determining the degree of these changes were not established. Aim. To evaluate the effect of incretin mimetic treatment of different duration on morphological and functional features of pancreatic α- and β-cells of 12-month-old rats with type 2 diabetes mellitus. Method. Streptozotocin-nicotinamide-induced type 2 diabetes mellitus was modeled in 12-month-old rats receiving a high-fat diet. The rats were treated with incretin mimetics, a GLP-1 receptor antagonist (Liraglutide) or a DPP-4 inhibitor (Vildagliptin) for 4, 10 or 24 weeks. Paraffin sections of the pancreas were stained with hematoxylin-eosin to evaluate the tissue microstructure. An immunohistochemical (IHC) study was performed using glucagon and insulin antibodies (Abcam) with a Thermo Autostainer 720 IHC instrument. After the IHC procedure, nuclei were additionally stained with hematoxylin using a Leica ST5020 stainer for histological micropreparations. Results. Untreated diabetes mellitus resulted in decreased numbers of α- and β-cells at all timepoints of observation. The treatments with Liraglutide and Vildagliptin recovered the pools of α- and β-cells. Significant differences of both treated and untreated diabetic groups from the control group in the number of α- and β-cells remained at all timepoints of observation. In the Liraglutide group at 4 weeks, the number of α-cells became comparable with the control group, but the number of β-cells remained lower. At 10 and 24 weeks of treatment, statistically significant differences between the control group and the Liraglutide or Vildagliptin treatment groups in the number of α- and β-cells were not observed. Conclusion. The results of the study suggested that the incretin mimetic therapy provided recovery of both α and β-cell pools in the pancreas.