In type 1 diabetes mellitus, the primary pathological alterations in the endocrine apparatus arise from the progressive loss of beta-cells, whereas beta-cell dysfunction is the key pathogenic factor in type 2 diabetes mellitus.

The aim of this study was to perform a quantitative assessment of the pancreatic islet architecture in normotensive Wistar rats under conditions of streptozotocin-induced diabetes mellitus, during hypoxic training, and in spontaneously hypertensive rats (SHRs).

Materials and methods. The experiment was conducted on 35 albino Wistar rats and 10 SHRs aged 5–6 months. The animals were divided into four groups: Group 1 (n = 10) – control Wistar rats; Group 2 (n = 15) – Wistar rats with streptozotocin-induced diabetes mellitus by a single intraperitoneal injection of streptozotocin (Sigma-Chemical, USA) at a dose of 50 mg/kg dissolved in 0.5 mL of 0.2 M citrate buffer (pH = 4.5). Only animals with fasting blood glucose exceeded 10.0 mmol/L at week 4 after streptozotocin administration were included in the study. Group 3 (n = 10) – SHR rats with hereditary arterial hypertension; Group 4 (n = 10) – Wistar rats subjected to a 15-day hypoxic training regimen according to the protocol: 15 consecutive days, 6 hours daily during days 1–5 at simulated altitudes ranging from 1 to 5 kilometers above sea level followed by 10 days at 6 km above sea level in a barochamber. Insulin and glucagon in pancreatic islet cells were detected using the immunofluorescence method with Insulin Antibody, clone 2D11-H5 (sc-8033 AF546), and Glucagon Antibody, clone K79bB10 (sc-57171 FITC) (Santa Cruz Biotechnology, USA). Immunofluorescent imaging was performed using an AxioImager-M2 fluorescence microscope (Carl Zeiss, Germany) equipped with an AxioCam-HRm digital camera (Carl Zeiss, Germany).

Results. In control Wistar rats, the specific density of pancreatic islets in the pancreas was 230 ± 3 cm–2. The islet structure was predominantly composed of small islets, while other types of islets, including solitary endocrinocytes, exhibited approximately equal distribution densities. Induction of experimental diabetes in Wistar rats by a single streptozotocin injection led to a reduction in the total number of islets to 117 ± 5 cm–2, i. e., a twofold decrease compared to the control group. Within the structure of the endocrine apparatus, nearly 50 % were small islets, the number of which exceeded that of control rats by 17 %, whereas the number of larger islets was significantly reduced. The genetic factor leading to hereditary hypertension in SHRs caused a 40 % decline in islet density (140 ± 3 cm–2) compared to controls, which nevertheless remained 10 % higher than in diabetic animals (p < 0.05), partially explaining the maintenance of normoglycemia in SHRs. Prolonged hypoxic training in Wistar rats did not significantly alter the total number of islets (241 ± 5 cm–2) but increased the number of both β+/α– and β–/α+ islets, as well as solitary endocrinocytes by 31 % (p < 0.05) compared to controls.

Conclusions. The endocrine pancreas is composed predominantly of “classical” islets containing beta- and alpha-cells. Small islets (≤1500 μm2) constituted approximately one-third of all islets. The total specific density of islets in control and hypoxia-trained Wistar rats was nearly twice that of diabetic or hypertensive SHRs. Clusters of solitary alpha-endocrinocytes were fourfold more numerous than solitary beta-endocrinocytes. In the pancreas of normal Wistar rats, an equal number of small islets with β+/α− and β−/α+ phenotypes were found. Pancreatic islet β−/α+ phenotype predominated in diabetic rats, whereas in hypoxia-trained Wistar rats, the population of β+/α− islets was sixfold higher than that of islets with β−/α+ phenotype, and this phenotype was absent in diabetic rats.