β3-adrenoceptor mediates β3-selective agonist-induced effects on energy expenditure, insulin secrtion and food intake
AbstractRecent studies suggest that type 2 diabetes, which is usually associated with obesity, also involves defective energy expenditure, specifically fat oxidation in skeletal muscle. Skeletal muscle is a major site of fatty acid and glucose disposal. β-adrenoceptor (β-AR) agonists have previously
been shown to stimulate glucose uptake in isolated skeletal muscle, stimulate lipolysis and increase energy expenditure. This work was designed to study the β3-AR as a potential target of anti-diabetic control in rodents using BRL37344. Energy expenditure induced by BRL37344 in
β3-AR knockout mice and wild type litter mates as control, were studied. Mice were dosed with saline or BRL37344 (1mg/kg, i.p). Energy expenditure in mice was measured by open-circuit, indirect calorimetry over twenty four hours. In another set of mice, similar dose of BRL37344 or
saline (vehicle) were given. After three hours, mice were sacrificed and plasma collected for the determination of glucose, triglycerides, non-esterified fatty acids, insulin and leptin. BRL37344 did not induce a significant change in energy expenditure in both the β3-AR knockout mice and the wild type. Also the lipolytic effect of BRL37344 was non significant. However, there was a significant 52% decrease in plasma glucose in the knockout mice and a 42% decrease in the wild type. This was consistent with the four fold increase in insulin secretion in the knockout and a
two fold increase in the wild type. There was also a significant increase in plasma leptin in the knockout mice as compared to the wild type. Improved insulin sensitivity and decreased blood glucose, induced by BRL37344 imply β3-AR is a potential target for diabetes and obesity control, at least in the rodents.