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Media type:
E-Article
Title:
β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes
Contributor:
Butler, Alexandra E.;
Janson, Juliette;
Bonner-Weir, Susan;
Ritzel, Robert;
Rizza, Robert A.;
Butler, Peter C.
Published:
American Diabetes Association, 2003
Published in:
Diabetes, 52 (2003) 1, Seite 102-110
Language:
English
DOI:
10.2337/diabetes.52.1.102
ISSN:
0012-1797;
1939-327X
Origination:
Footnote:
Description:
<jats:p>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.</jats:p>