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Biochem Biophys Res Commun. 2005 Sep 2;334(3):764-8.

The transcription factor Stat3 is dispensable for pancreatic beta-cell development and function.

Author information

1
Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. Gorogawa, Y. Fujitani, H. Kaneto, Y. Hazama, H. Watada, Y. Miyamoto, K. Takeda, S. Akira, M. Magnuson, Y. Yamasaki, Y. Kajimoto, M. Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. Biophys. Res. Commun. 319 (2004) 1159; Y. Cui, L. Huang, F. Elefteriou, G. Yang, J. Shelton, J. Giles, O. Oz, T. Pourbahrami, C. Lu, J. Richardson, G. Karsenty, C. Li, Essential role of STAT3 in body weight and glucose homeostasis, Mol. Cell. Biol. 24 (2004) 258]. However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. We have addressed this issue through the inactivation of Stat3 from pancreatic beta-cells using a Pdx1-Cre transgene. Complete loss of Stat3 was observed in islets from mice, which carry two floxed Stat3 alleles and the Pdx1-Cre transgene. However, these mice did not develop glucose intolerance or obesity over a period of 6 months, demonstrating that Stat3 is dispensable for the generation and physiology of beta-cells. Similarly, mice that express only the Pdx1-Cre transgene display a normal physiology. In contrast, mice that expressed only the RIP-Cre transgene developed glucose intolerance as early as 6 weeks of age. The finding that RIP-Cre transgenic mice in a C57B/6 dominated background develop glucose intolerance is important as this line has been used in several studies.

PMID:
16026757
DOI:
10.1016/j.bbrc.2005.06.162
[Indexed for MEDLINE]

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