Metabolic alterations associated with the antidiabetic effect of beta 3-adrenergic receptor agonists in obese mice
1995
Arbeeny, C.M. | Meyers, D.S. | Hillyer, D.E. | Bergquist, K.E.
Treatment of obese (ob/ob) mice with the beta3-adrenergic receptor (beta3-AR) agonist BRL35135 (1 mg.kg body wt-1.day-1 for 20 days) normalized plasma glucose levels and significantly decreased plasma insulin and nonesterified fatty acid levels. The time frame for the hypoglycemic effect, which reached a maximum after 10 days of treatment, paralleled an increase in brown adipose tissue DNA and protein content. The basal level of mRNA for the beta3-AR and mitochondrial uncoupling protein was found to be markedly decreased in the ob/ob animals relative to the lean group. Chronic treatment of ob/ob mice for 20 days resulted in a twofold increase in beta3-AR mRNA and a fivefold increase in uncoupling protein mRNA in brown adipose tissue relative to the placebo group. These findings indicate that chronic treatment of ob/ob animals with a beta3-AR agonist results in proliferation of brown adipose tissue, with an upregulation of the beta3-AR, which is associated with a decrease in plasma glucose, insulin, and nonesterified fatty acid levels.
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