Insulin protects against type 1 diabetes mellitus-induced ultrastructural abnormalities of pancreatic islet microcirculation.

Abstract

Pancreatic islet microcirculation, consisting of pancreatic islet microvascular endothelial cells (IMECs) and pericytes (IMPCs), provides crucial support for the physiological function of pancreatic islet. Emerging evidence suggests that pancreatic islet microcirculation is impaired in type 1 diabetes mellitus (T1DM). Here, we investigated the potential ultrastructural protective effects of insulin against streptozotocin (STZ)-induced ultrastructural abnormalities of the pancreatic islet microcirculation in T1DM mouse model. For this purpose, pancreatic tissues were collected from control, STZ-induced T1DM and insulin-treated mice, and a pancreatic IMECs cell line (MS1) was cultured under control, 35 mM glucose with or without 10−8 M insulin conditions. Transmission and scanning electron microscopies were employed to evaluate the ultrastructure of the pancreatic islet microcirculation. We observed ultrastructural damage to IMECs and IMPCs in the type 1 diabetic group, as demonstrated by destruction of the cytoplasmic membrane and organelles (mainly mitochondria), and this damage was substantially reversed by insulin treatment. Furthermore, insulin inhibited collagenous fiber proliferation and alleviated edema of the widened pancreatic islet exocrine interface in T1DM mice. We conclude that insulin protects against T1DM-induced ultrastructural abnormalities of the pancreatic islet microcirculation.