The transcription factor Stat3 is dispensable for pancreatic beta-cell development and function
Ji-Yeon Lee1, Lothar Hennighausen
1Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Biochemical and Biophysical Research Communications
|July 20, 2005
Summary
Signal transducer and activator of transcription 3 (Stat3) is not essential for pancreatic beta-cell function. Inactivating Stat3 in beta-cells did not cause glucose intolerance, indicating Stat3
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Signal transducer and activator of transcription 3 (Stat3) is activated by cytokines like leptin and gp130.
- Previous studies using RIP-Cre transgenes showed Stat3 inactivation caused glucose intolerance and obesity.
- RIP-Cre is also expressed in the hypothalamus, confounding whether defects were due to beta-cell or hypothalamic Stat3 loss.
Purpose of the Study:
- To determine if Stat3 is essential for pancreatic beta-cell generation and physiology.
- To differentiate the roles of Stat3 in beta-cells versus the hypothalamus in metabolic regulation.
Main Methods:
- Generated mice with Stat3 specifically inactivated in pancreatic beta-cells using a Pdx1-Cre transgene.
- Analyzed Stat3 expression in islets of mice with floxed Stat3 alleles and Pdx1-Cre.
- Assessed glucose tolerance and obesity in these mice over 6 months.
- Compared results with mice expressing only Pdx1-Cre or RIP-Cre transgenes.
Main Results:
- Complete loss of Stat3 was confirmed in islets of Pdx1-Cre; Stat3-floxed mice.
- These mice did not develop glucose intolerance or obesity.
- RIP-Cre transgenic mice, but not Pdx1-Cre mice, exhibited glucose intolerance.
Conclusions:
- Stat3 is dispensable for the generation and normal physiology of pancreatic beta-cells.
- The metabolic defects observed in prior RIP-Cre studies are likely due to hypothalamic Stat3 deletion.
- This research clarifies the specific role of Stat3 in beta-cells versus other tissues in glucose homeostasis.
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