Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects

Diabetes. 2004 Mar;53(3):624-32. doi: 10.2337/diabetes.53.3.624.

Abstract

Type 2 diabetic subjects manifest both disordered insulin action and abnormalities in their pancreatic islet cells. Whether the latter represents a primary defect or is a consequence of the former is unknown. To examine the beta-cell mass and function of islets from type 2 diabetic patients directly, we isolated islets from pancreata of type 2 diabetic cadaveric donors (n = 14) and compared them with islets from normal donors (n = 14) matched for age, BMI, and cold ischemia time. The total recovered islet mass from type 2 diabetic pancreata was significantly less than that from nondiabetic control subjects (256,260 islet equivalents [2,588 IEq/g pancreas] versus 597,569 islet equivalents [6,037 IEq/g pancreas]). Type 2 diabetic islets were also noted to be smaller on average, and histologically, islets from diabetic patients contained a higher proportion of glucagon-producing alpha-cells. In vitro study of islet function from diabetic patients revealed an abnormal glucose-stimulated insulin release response in perifusion assays. In addition, in comparison with normal islets, an equivalent number of type 2 diabetic islets failed to reverse hyperglycemia when transplanted to immunodeficient diabetic mice. These results provide direct evidence for abnormalities in the islets of type 2 diabetic patients that may contribute to the pathogenesis of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / pathology*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Humans
  • Islets of Langerhans / cytology
  • Islets of Langerhans / pathology*
  • Islets of Langerhans / physiology
  • Islets of Langerhans Transplantation / physiology
  • Middle Aged
  • Organ Size
  • Patient Selection
  • Reference Values
  • Retrospective Studies