Betacellulin overexpression in transgenic mice improves glucose tolerance and enhances insulin secretion by isolated islets in vitro

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:299

Article

Dahlhoff, M.¹  Dames, P. M.²  Lechner, A.²  Herbach, N.³  van Buerck, L.³  Wanke, R.³  Wolf, E.^1,4  Schneider, M. R.¹ 

[1] Ludwig Maximilians Univ Munchen, Gene Ctr, Inst Mol Anim Breeding & Biotechnol, D-81377 Munich, Germany

[2] Ludwig Maximilians Univ Munchen, Klinikum Grosshadern, Med Klin 2, D-81377 Munich, Germany

[3] Ludwig Maximilians Univ Munchen, Inst Vet Pathol, D-81377 Munich, Germany

[4] Ludwig Maximilians Univ Munchen, Gene Ctr, LAFUGA, D-81377 Munich, Germany

关键词: Betacellulin;    EGFR;    Transgenic mice;    Glucose metabolism;    Glucose tolerance test;   

DOI  :  10.1016/j.mce.2008.11.022

来源: Elsevier

【 摘 要 】

Betacellulin (BTC), a ligand of the epidermal growth factor receptor, has been shown to promote growth and differentiation of pancreatic R-cells and to improve glucose metabolism in experimental diabetic rodent models. We employed transgenic mice (BTC-tg) to investigate the effects of long-term BTC overabundance on islet structure and glucose metabolism. Expression of BTC is increased in transgenic islets, which show normal structure and distribution of the different endocrine cell types, without pathological alterations. BTC-tg mice exhibit lower fasted glucose levels and improved glucose tolerance associated with increased glucose-induced insulin secretion. Surprisingly, quantitative stereological analyses revealed that, in spite of increased cell proliferation, the islet and P-cell volumes were unchanged in BTC-tg mice, suggesting enhanced cell turnover. Insulin secretion in vitro was significantly higher in transgenic islets in medium containing high glucose (11.2 or 16.7 mM) as compared to control islets. Our results demonstrate that long-term BTC overabundance does not alter pancreatic islet structure and P-cell mass, but enhances glucose-induced insulin secretion in vivo as well as in vitro. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

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