Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects.
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.
Department of Surgery, Harrison Department of Surgical Research, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Shaoping
S
Deng
Marko
M
Vatamaniuk
Xiaolun
X
Huang
Nicolai
N
Doliba
Moh-Moh
MM
Lian
Adam
A
Frank
Ergun
E
Velidedeoglu
Niraj M
NM
Desai
Brigitte
B
Koeberlein
Bryan
B
Wolf
Clyde F
CF
Barker
Ali
A
Naji
Franz M
FM
Matschinsky
James F
JF
Markmann
D017668:Age of Onset; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000473:pathology* / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000502:physiology; D008875:Middle Aged; D009929:Organ Size; D018579:Patient Selection; D012016:Reference Values; D012189:Retrospective Studies