guanosine-diphosphate and ciglitazone

Chronic dietary administration of the oral hypoglycaemic ciglitazone (3 g/day for 14-28 days) to lean, non-diabetic CDl mice resulted in increased brown adipose tissue mitochondrial GDP binding and a marked increase in the thermic effect of the beta-adrenoceptor agonist BRL 26830A. However, ciglitazone was not itself thermogenic after an acute dose, nor did it raise resting metabolic rate during chronic dietary dosing.

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Calorimetry; Energy Metabolism; Female; Guanosine Diphosphate; Hypoglycemic Agents; Mice; Thiazoles; Thiazolidinediones

Genetically obese (ob/ob) mice develop a marked insulin resistance in brown adipose tissue soon after weaning, and this is paralleled by a fall in the acute activation of the mitochondrial proton conductance pathway in the tissue on cold exposure. Treatment of ob/ob mice with ciglitazone, a new oral hypoglycaemic, led to a restoration of insulin sensitivity in brown adipose tissue. The amelioration of insulin resistance was accompanied by a normalization of the acute, cold-induced increase in mitochondrial GDP binding. These results support the hypothesis that the development of insulin resistance in brown adipose tissue is an important factor in the impaired thermogenic responsiveness of obese mice.

Topics: Adipose Tissue, Brown; Animals; Cold Temperature; Guanosine Diphosphate; Insulin; Insulin Resistance; Lipids; Male; Mice; Mice, Obese; Mitochondria; Thiazoles; Thiazolidinediones