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Diabetes 54:3490-3495, 2005
© 2005 by the American Diabetes Association, Inc.

The Lack of ß-Adrenoceptors Results in Enhanced Insulin Sensitivity in Mice Exhibiting Increased Adiposity and Glucose Intolerance

Cédric Asensio1,2, Maria Jimenez3, Françoise Kühne1, Françoise Rohner-Jeanrenaud1,2, and Patrick Muzzin1

1 Department of Cell Physiology and Metabolism, Medical University Centre, Geneva, Switzerland
2 Department of Internal Medicine, Division of Endocrinology, Diabetology and Nutrition, Medical University Centre, Geneva, Switzerland
3 Department of Medical Biochemistry, Medical University Centre, Geneva, Switzerland

We and others have previously shown that triple knockout mice lacking the ß1/ß2/ß3-adrenoceptors (ß-less mice) developed a progressive obesity at adulthood. Here, we studied the glucose homeostasis in ß-less mice before the onset of obesity. We show that ß-less mice have increased fat mass and are glucose intolerant. In addition, we observed that ß-less mice have impaired glucose-induced insulin secretion and exhibit an increase in liver PEPCK gene expression in the fed state, suggesting that they have increased gluconeogenesis. Although these characteristics are usually associated with insulin resistance, ß-less mice exhibit enhanced insulin sensitivity during insulin tolerance tests. This is keeping with the results obtained during euglycemic-hyperinsulinemic clamps showing that ß-less mice display increased insulin responsiveness with normal suppression of hepatic glucose production. Altogether, our results suggest that an intact ß-adrenergic system is required to regulate overall glucose homeostasis and, in particular, insulin-mediated glucose uptake, most likely at the level of muscles and adipose tissue.

Address correspondence and reprint requests to Cédric Asensio, Department of Neurology, University of California at San Francisco, Genentech Hall, 600 16th St., 94143-2140, San Francisco, CA. E-mail: asensio{at}itsa.ucsf.edu

Abbreviations: GTT, glucose tolerance test; ITT, insulin tolerance test


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Copyright © 2005 by the American Diabetes Association.