title: The pancreatic beta cell is a key site for mediating the effects of leptin on glucose homeostasis.
abstract: 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 beta cells. To study this further in mice, we disrupted the signaling domain of the leptin receptor gene in beta 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 beta cell function, independent of pathways controlling food intake. These data suggest that defects in this adipoinsular axis could contribute to diabetes associated with obesity.
authors.affiliation: Laboratory of Molecular and Cellular Medicine, Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Covey
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Wideman
authors.forename: Christine
authors.initials: C
authors.lastname: McDonald
authors.forename: Suraj
authors.initials: S
authors.lastname: Unniappan
authors.forename: Frank
authors.initials: F
authors.lastname: Huynh
authors.forename: Ali
authors.initials: A
authors.lastname: Asadi
authors.forename: Madeleine
authors.initials: M
authors.lastname: Speck
authors.forename: Travis
authors.initials: T
authors.lastname: Webber
authors.forename: Streamson C
authors.initials: SC
authors.lastname: Chua
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kieffer
mesh_terms: D000818:Animals; D004435:Eating; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors
chemical_list: D007328:Insulin; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D005947:Glucose