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

Abstract

We and others have previously shown that triple knockout mice lacking the β₁/β₂/β₃-adrenoceptors (β-less mice) developed a progressive obesity at adulthood. Here, we studied the glucose homeostasis in β-less mice before the onset of obesity. We show that β-less mice have increased fat mass and are glucose intolerant. In addition, we observed that β-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, β-less mice exhibit enhanced insulin sensitivity during insulin tolerance tests. This is keeping with the results obtained during euglycemic-hyperinsulinemic clamps showing that β-less mice display increased insulin responsiveness with normal suppression of hepatic glucose production. Altogether, our results suggest that an intact β-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.