In:
Diabetes, American Diabetes Association, Vol. 52, No. 1 ( 2003-01-01), p. 102-110
Abstract:
Type 2 diabetes is characterized by impaired insulin secretion. Some but not all studies suggest that a decrease in β-cell mass contributes to this. We examined pancreatic tissue from 124 autopsies: 91 obese cases (BMI & gt;27 kg/m2; 41 with type 2 diabetes, 15 with impaired fasting glucose [IFG], and 35 nondiabetic subjects) and 33 lean cases (BMI & lt;25 kg/m2; 16 type 2 diabetic and 17 nondiabetic subjects). We measured relative β-cell volume, frequency of β-cell apoptosis and replication, and new islet formation from exocrine ducts (neogenesis). Relative β-cell volume was increased in obese versus lean nondiabetic cases (P = 0.05) through the mechanism of increased neogenesis (P & lt; 0.05). Obese humans with IFG and type 2 diabetes had a 40% (P & lt; 0.05) and 63% (P & lt; 0.01) deficit and lean cases of type 2 diabetes had a 41% deficit (P & lt; 0.05) in relative β-cell volume compared with nondiabetic obese and lean cases, respectively. The frequency of β-cell replication was very low in all cases and no different among groups. Neogenesis, while increased with obesity, was comparable in obese type 2 diabetic, IFG, or nondiabetic subjects and in lean type 2 diabetic or nondiabetic subjects. However, the frequency of β-cell apoptosis was increased 10-fold in lean and 3-fold in obese cases of type 2 diabetes compared with their respective nondiabetic control group (P & lt; 0.05). We conclude that β-cell mass is decreased in type 2 diabetes and that the mechanism underlying this is increased β-cell apoptosis. Since the major defect leading to a decrease in β-cell mass in type 2 diabetes is increased apoptosis, while new islet formation and β-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 diabetes, because this approach might actually reverse the disease to a degree rather than just palliate glycemia.
Type of Medium:
Online Resource
ISSN:
0012-1797
,
1939-327X
DOI:
10.2337/diabetes.52.1.102
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2003
detail.hit.zdb_id:
1501252-9
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