Glucagon-like peptide I (GLP-I) stimulates glucosedependent insulin secretion and inhibits food intake in the central nervous system. Because leptin reduces food intake but inhibits insulin secretion, we examined leptin action in mice with a null mutation in the GLP-I receptor. Intracerebroventricular leptin administration inhibited food intake in both wild-type and GLP-I receptor (GLP-IR) −/− mice, and daily intraperitoneal administration of leptin for 2 weeks produced comparable reductions in food intake and body weight in control and GLP-IR −/− mice. Glucose tolerance was improved in both wild-type and GLP-IR −/− mice, whether pair fed or leptin treated; however, blood sugars were significantly lower in the leptin-treated GLPIR −/− mice following oral glucose challenge (P < 0.01). Glucose-stimulated insulin was reduced in both pair-fed and leptin-treated mice (P < 0.01–0.001); however, insulin levels were significantly lower in leptin-treated versus pairfed GLP-IR −/− mice (P < 0.01). A single leptin injection had no effect on glucose tolerance in GLPIR −/− mice, but decreased hepatic PEPCK mRNA in both wild-type and GLP-IR −/− mice. The improvement in blood glucose excursion, despite lower levels of glucose-stimulated insulin in lean leptin-treated GLP-IR −/− mice, suggests that leptin may have beneficial effects on control of blood glucose in the absence of obesity. Furthermore, the greater effects of leptin on glucose and insulin in leptin-treated versus pair-fed GLP-IR −/− mice raises the possibility that disruption of GLP-I signaling modifies the sensitivity to leptin in vivo.
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Original Articles|
December 01 1997
Leptin Sensitivity in Nonobese Glucagon-Like Peptide I Receptor −/− Mice
Louise A Scrocchi;
Louise A Scrocchi
Departments of Medicine, Banting and Best Diabetes Centre, The Toronto Hospital, University of Toronto
Toronto, Canada
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Theodore J Brown;
Theodore J Brown
Reproductive Biology, Banting and Best Diabetes Centre, The Toronto Hospital, University of Toronto
Toronto, Canada
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Daniel J Drucker
Daniel J Drucker
Departments of Medicine, Banting and Best Diabetes Centre, The Toronto Hospital, University of Toronto
Toronto, Canada
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Address correspondence and reprint requests to Daniel Drucker, The Toronto Hospital, 200 Elizabeth St. CCRW3-838, Toronto M5G 2C4, Canada. E-mail: d.drucker@utoronto.ca.
Diabetes 1997;46(12):2029–2034
Article history
Received:
April 22 1997
Revision Received:
August 07 1997
Accepted:
August 07 1997
Citation
Louise A Scrocchi, Theodore J Brown, Daniel J Drucker; Leptin Sensitivity in Nonobese Glucagon-Like Peptide I Receptor −/− Mice. Diabetes 1 December 1997; 46 (12): 2029–2034. https://doi.org/10.2337/diab.46.12.2029
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