Insulin improves β-cell function in glucose-intolerant rat models induced by feeding a high-fat diet

Insulin therapy has been shown to contribute to extended glycemia remission in newly diagnosed patients with type 2 diabetes mellitus. This study investigated the effects of insulin treatment on pancreatic lipid content, and beta-cell apoptosis and proliferation in glucose-intolerant rats to explore the protective role of insulin on beta-cell function. A rat glucose-intolerant model was induced by streptozotocin and a high-fat diet. Plasma and pancreatic triglycerides, free fatty acids, and insulin were measured; and pancreatic beta-cell cell apoptosis and proliferation were detected by a propidium iodide cell death assay and immunofluorescence for proliferating cell nuclear antigen. Relative beta-cell area was determined by immunohistochemistry for insulin, whereas insulin production in pancreas was assessed by reverse transcriptase polymerase chain reaction. Islet beta-cell secreting function was assessed by the index Delta I30/Delta G30. Glucose-intolerant rats had higher pancreatic lipid content, more islet beta-cell apoptosis, lower beta-cell proliferation, and reduced beta-cell area in pancreas when compared with controls. Insulin therapy reduced blood glucose, inhibited pancreatic lipid accumulation and islet beta-cell apoptosis, and increased beta-cell proliferation and beta-cell area in glucose-intolerant rats. Furthermore, impaired insulin secretion and insulin production in glucose-intolerant rats were improved by insulin therapy. Insulin can preserve beta-cell function by protecting islets from glucotoxicity and lipotoxicity. It can also ameliorate beta-cell area by enhancing beta-cell proliferation and reducing beta-cell apoptosis. (C) 2011 Elsevier Inc. All rights reserved.