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Horm Metab Res 2011; 43(5): 306-311
DOI: 10.1055/s-0031-1271817
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Reduced Proliferation and a High Apoptotic Frequency of Pancreatic Beta Cells Contribute to Genetically-determined Diabetes Susceptibility of db/db BKS Mice

R. Puff1 , P. Dames1 , M. Weise1 , 2 , B. Göke1 , J. Seissler2 , K. G. Parhofer1 , A. Lechner1 , 2
  • 1Ludwig-Maximilians-Universität, Klinikum Großhadern, Medizinische Klinik 2, München, Germany
  • 2Ludwig-Maximilians-Universität, Medizinische Klinik – Innenstadt, München, Germany
Further Information

Publication History

received 15.11.2010

accepted 02.02.2011

Publication Date:
16 March 2011 (online)

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Abstract

Leptin receptor-deficient db/db mice are a commonly used research model and it is known that the genetic background, on which the mutation is bred, modulates the phenotype. While diabetes-resistant strains sustain near normal glycemia and hyperinsulinemia, susceptible backgrounds develop overt hyperglycemia and islet involution. We hypothesized that genetically-determined differences in the proliferative capacity and the apoptotic frequency of pancreatic beta cells contribute to this phenotypic disparity. We studied C57BLKS/J (BKS; diabetes-susceptible) and C57BL/6 (B6; diabetes-resistant) db/db mice and heterozygous controls from 5 to 12 weeks of age. Body weight, fasting blood glucose, plasma insulin, HOMA-IR, alpha cell mass, beta cell mass, proliferation and apoptosis were measured. Comparable insulin resistance developed in the 2 db/db strains, which was well compensated for on both genetic backgrounds until 7 weeks of age. As expected, the BKS mice became hyperglycemic at 9 weeks. Beta cell proliferation was initially increased in both db/db strains but decreased rapidly in the BKS mice with advancing age. The rate of beta cell apoptosis was already higher in prediabetic BKS mice than in their B6 counterparts. Beta cell mass increased continuously in the B6 strain until 12 weeks of age, but declined from 7 weeks onwards in BKS. An age-dependent decline of beta cell proliferation and an increased rate of beta cell apoptosis already in the prediabetic state probably contribute to the diabetes susceptibility of db/db BKS mice. These factors could also play a role in the genetic predisposition for type 2 diabetes in humans.

Key words

NIDDM - type 2 diabetes - BrdU - TUNEL-staining - B6 - BKS - db/db mouse

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Correspondence

A. Lechner

Medizinische Klinik – Innenstadt

Ziemssenstraße 1

80336 München

Germany

Phone: +49/89/5160 2185

Fax: +49/89/5160 3374

Email: andreas.lechner@med.uni-muenchen.de

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