TY - JOUR
T1 - Structural and Functional Abnormalities in the Islets Isolated from Type 2 Diabetic Subjects
AU - Deng, Shaoping
AU - Vatamaniuk, Marko
AU - Huang, Xiaolun
AU - Doliba, Nicolai
AU - Lian, Moh Moh
AU - Frank, Adam
AU - Velidedeoglu, Ergun
AU - Desai, Niraj M.
AU - Koeberlein, Brigitte
AU - Wolf, Bryan
AU - Barker, Clyde F.
AU - Naji, Ali
AU - Matschinsky, Franz M.
AU - Markmann, James F.
PY - 2004/3
Y1 - 2004/3
N2 - 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 β-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 α-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.
AB - 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 β-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 α-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.
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U2 - 10.2337/diabetes.53.3.624
DO - 10.2337/diabetes.53.3.624
M3 - Article
C2 - 14988246
AN - SCOPUS:10744222060
SN - 0012-1797
VL - 53
SP - 624
EP - 632
JO - Diabetes
JF - Diabetes
IS - 3
ER -