The pancreatic β cell is a key site for mediating the effects of leptin on glucose homeostasis

Scott D. Covey, Rhonda D. Wideman, Christine McDonald, Suraj Unniappan, Frank Huynh, Ali Asadi, Madeleine Speck, Travis Webber, Streamson C. Chua, Timothy J. Kieffer

Research output: Contribution to journalArticlepeer-review

148 Scopus citations


The hormone leptin plays a crucial role in maintenance of body weight and glucose homeostasis. This occurs through central and peripheral pathways, including regulation of insulin secretion by pancreatic β cells. To study this further in mice, we disrupted the signaling domain of the leptin receptor gene in β cells and hypothalamus. These mice develop obesity, fasting hyperinsulinemia, impaired glucose-stimulated insulin release, and glucose intolerance, similar to leptin receptor null mice. However, whereas complete loss of leptin function causes increased food intake, this tissue-specific attenuation of leptin signaling does not alter food intake or satiety responses to leptin. Moreover, unlike other obese models, these mice have reduced fasting blood glucose. These results indicate that leptin regulation of glucose homeostasis extends beyond insulin sensitivity to influence β cell function, independent of pathways controlling food intake. These data suggest that defects in this adipoinsular axis could contribute to diabetes associated with obesity.

Original languageEnglish (US)
Pages (from-to)291-302
Number of pages12
JournalCell metabolism
Issue number4
StatePublished - Oct 2006
Externally publishedYes



ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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