β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes

Alexandra E. Butler, Juliette Janson, Susan Bonner-Weir, Robert Ritzel, Robert A. Rizza, Peter C. Butler

Research output: Contribution to journalArticle

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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 > 27 kg/m 2; 41 with type 2 diabetes, 15 with impaired fasting glucose [IFG], and 35 nondiabetic subjects) and 33 lean cases (BMI <25 kg/m 2; 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 < 0.05). Obese humans with IFG and type 2 diabetes had a 40% (P < 0.05) and 63% (P < 0.01) deficit and lean cases of type 2 diabetes had a 41% deficit (P < 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 < 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.

Original languageEnglish (US)
Pages (from-to)102-110
Number of pages9
JournalDiabetes
Volume52
Issue number1
DOIs
StatePublished - Jan 1 2003

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Type 2 Diabetes Mellitus
Apoptosis
Cell Size
Fasting
Glucose
Islets of Langerhans
Autopsy
Obesity
Insulin
Control Groups

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Butler, A. E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R. A., & Butler, P. C. (2003). β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes, 52(1), 102-110. https://doi.org/10.2337/diabetes.52.1.102

β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. / Butler, Alexandra E.; Janson, Juliette; Bonner-Weir, Susan; Ritzel, Robert; Rizza, Robert A.; Butler, Peter C.

In: Diabetes, Vol. 52, No. 1, 01.01.2003, p. 102-110.

Research output: Contribution to journalArticle

Butler, AE, Janson, J, Bonner-Weir, S, Ritzel, R, Rizza, RA & Butler, PC 2003, 'β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes', Diabetes, vol. 52, no. 1, pp. 102-110. https://doi.org/10.2337/diabetes.52.1.102
Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003 Jan 1;52(1):102-110. https://doi.org/10.2337/diabetes.52.1.102
Butler, Alexandra E. ; Janson, Juliette ; Bonner-Weir, Susan ; Ritzel, Robert ; Rizza, Robert A. ; Butler, Peter C. / β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. In: Diabetes. 2003 ; Vol. 52, No. 1. pp. 102-110.
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