The pancreatic beta cell is a key site for mediating the effects of leptin on glucose homeostasis.
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.
Covey
Scott D
SD
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.
Wideman
Rhonda D
RD
McDonald
Christine
C
Unniappan
Suraj
S
Huynh
Frank
F
Asadi
Ali
A
Speck
Madeleine
M
Webber
Travis
T
Chua
Streamson C
SC
Kieffer
Timothy J
TJ
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
D007328:Insulin; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D005947:Glucose