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Diabetes 53:624-632, 2004
© 2004 by the American Diabetes Association, Inc.

Structural and Functional Abnormalities in the Islets Isolated From Type 2 Diabetic Subjects

Shaoping Deng1, Marko Vatamaniuk2,3, Xiaolun Huang1, Nicolai Doliba2,3, Moh-Moh Lian1, Adam Frank1, Ergun Velidedeoglu1, Niraj M. Desai1, Brigitte Koeberlein1, Bryan Wolf4, Clyde F. Barker1, Ali Naji1, Franz M. Matschinsky2,3, and James F. Markmann1

1 Department of Surgery, Harrison Department of Surgical Research, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
2 Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
3 Penn Diabetes Center, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
4 Department of Pathology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania

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 ß-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.

Address correspondence and reprint requests to James F. Markmann, MD, PhD, Department of Surgery, Hospital of the University of Pennsylvania, 4th floor Silverstein, 3400 Spruce St., Philadelphia, PA 19104. E-mail: james.markmann{at}uphs.upenn.edu


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