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- Title
Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects.
- Authors
Deng, Shaoping; Vatamaniuk, Marko; Huang, Xiaolun; Doliba, Nicolai; Lian, Moh-Moh; Frank, Adam; Velidedeoglu, Ergun; Desai, Niraj M.; Koeberlein, Brigitte; Wolf, Bryan; Barker, Clyde F.; Naji, Ali; Matschinsky, Franz M.; Markmann, James F.
- 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.
- Subjects
HUMAN abnormalities; ISLANDS of Langerhans; DIABETES; PANCREATIC diseases; PANCREATIC secretions; PANCREAS; CARBOHYDRATE intolerance
- Publication
Diabetes, 2004, Vol 53, Issue 3, p624
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.53.3.624