Apolipoprotein A-I Stimulates Secretion of Insulin and Matrix Metalloproteinases by Islets of Langerhans

Abstract

The development of type 2 diabetes mellitus (DM2) is accompanied by impairments in lipid metabolism. These include the increase in serum levels of atherogenic fractions of very low-density (VLDL) and low-density lipoproteins (LDL), total cholesterol, triglycerides, and apoB. The level of antiatherogenic high density lipoproteins (HDL) and the content of apolipoprotein A-I (apoA-I) decreased. To study the effect of the observed metabolic changes on insulin secretion in vitro, we have used the islets of Langerhans isolated from the rat pancreas. It has been found that incubation of the islets in the presence of serum of obese patients and patients with decompensated DM2 leads to a 2.4-fold and 5.0-fold decrease in insulin secretion, respectively. On the contrary, addition of HDL to the incubation medium caused a 3.4-fold increase in the insulin secretion. A similar effect was observed in the presence of apoA-I, the main protein component of HDL. In the presence of apoA-I, the extracellular activity of matrix metalloproteinases (MMPs) demonstrated a 10-fold increase. The addition of LDL and VLDL to the islets did not change the insulin secretion and MMP activity. Our results emphasize an important role of HDL and apoA-I in the regulation of the insulin secretion by β-cells and the MMP activity in the islets of Langerhans.