brl-26830a and Diabetes-Mellitus

The anti-obesity and anti-diabetic actions of BRL 26830A, beta 3-adrenoceptor agonist, (2 mg/kg administered intramuscularly daily for 2 weeks) were evaluated in obese diabetic Yellow KK mice and C57B1 control mice. The following parameters were compared in the treated vs. control animals: brown adipose tissue (BAT) thermogenesis, resting metabolic rate (RMR), insulin receptors in adipocytes, and blood glucose and serum insulin levels during a glucose overloading test. BRL 26830A significantly increased BAT thermogenesis and RMR but it decreased the amount of white adipose tissue without affecting food intake. Those actions contributed to the mitigation of obesity in Yellow KK mice. BRL 26830A also increased the concentration of insulin receptors and decreased the levels of serum insulin and blood glucose during the glucose overloading test in Yellow KK mice. In the glucose overloading test performed one hour after BRL 26830A injection, insulin secretion was significantly increased and the blood glucose level was markedly decreased in both groups. These observations suggest that BRL 26830A possesses anti-obesity and anti-diabetic actions and consequently may be useful for treating obesity as well as non-insulin-dependent diabetes mellitus with obesity.

Topics: Adipose Tissue, Brown; Adrenergic beta-Agonists; Animals; Blood Glucose; Diabetes Mellitus; Disease Models, Animal; Ethanolamines; Guanosine Diphosphate; Insulin; Male; Mice; Mice, Inbred Strains; Mitochondria; Obesity; Organ Size; Oxygen Consumption; Proteins

The size and morphological characteristics of muscles from diabetic obese (db/db) mice and their normal lean littermates were investigated. The soleus muscles were similar in size in diabetic and normal mice but the biceps brachii and gastrocnemius were significantly lighter in the diabetic animals. In the biceps brachii the small size resulted from an overall reduction in fibre diameter, which was most acute in the fast white fibres, and an increase in the proportion of smaller fast intermediate fibres. Treatment of diabetic mice with BRL 26830 a thermogenic, beta-adrenoceptor agonist, restored the weight, fibre diameter and fibre type composition of the biceps brachii to that of lean littermates. This treatment also increased the weight of the gastrocnemius, together with its protein content. Since BRL 26830 restored normoglycaemia in the diabetic mice, without decreasing their body weight, we suppose that it improved insulin action in their muscles and this, in turn, stimulated muscle growth.

Topics: Adrenergic beta-Agonists; Animals; Body Temperature Regulation; Diabetes Mellitus; Diabetes Mellitus, Experimental; Ethanolamines; Female; Insulin Resistance; Mice; Mice, Inbred C57BL; Muscles; Obesity