Influence of norepinephrine and exercise on lipolysis in adipose tissue of diabetic rats

Abstract

Summary. The lipolytic effect of norepinephrine (NE) in adipose tissue in vitro was studied before and after exercise in non-fasted rats with severe, untreated streptozotocin diabetes. It was observed that: 1. NE in increasing concentrations stimulated glycerol release in vitro to an equal extent from the adipose tissue of nondiabetic and diabetic rats. However, the re-esterification of free fatty acids (FFA) in adipose tissue in vitro was decreased by NE in diabetic rats as compared to normal rats. 2. During exercise NE further decreased the re-esterification of FFA in vitro in adipose tissue of diabetic rats. 3. Exercise did not change NE-induced glycerol release in vitro in the adipose tissue of diabetic rats. 4. In diabetic animals the increase in plasma glycerol and FFA during exercise was correlated inversely with the NE-induced release of glycerol and FFA from the adipose tissue of the same animals after exercise. The lipolytic effect of NE is not significantly different in adipose tissue of diabetic and nondiabetic rats. By decreasing the re-esterification of FFA in vitro, NE is probably responsible for the observed increase in the release of FFA in vivo, a likely energy source in severely diabetic animals.Key words: Adipose tissue, catecholamines, diabetes, exercise, free fatty acids, glycerol, lipolysis, rat, streptozotocin.In untreated diabetic patients exercise induces a higher rise in plasma catecholamines [6,7] and a more intense lipid mobilization [5,13] than in nondiabetic subjects.The increased lipolysis in diabetic adipose tissue is at least partly due to the high level of circulating catecholamines [6]. Adequate insulin treatment decreases plasma catecholamines [6,7] and lipolysis [5] during exercise.It is hitherto unresolved whether the enhanced lipolysis in diabetes induced by exercise is due to lack of insulin and the associated rise in lipolytic hormones or whether exercise alters the sensitivity of diabetic adipose tissue to lipolytic hormones, e.g. to catecholamines. We have accordingly studied, in diabetic animals, the norepinephrine (NE)-induced release of glycerol and free fatty acids (FFA) in vitro before and after exercise and lipid mobilization in vivo during exercise. Materials and Methods RatsMale Sprague-Dawley rats, weighing 300 to 350 g were used. Streptozotocin (Upjohn & Co., lot 968L-GGS-118FJ) was freshly prepared in 0,1 molar citrate buffer, pH 4,5, and injected intravenously into fed animals in a dose of 65 mg/kg body weight. The rats were fed a normal commercial chow Iad libitum until the experiment, which started 42-48 h after the administration of streptozotocin. During this time the weight loss of untreated diabetic animals was 30 + 3 g (mean + SEM; n = 32), whereas control animals gained weight 9 + 2 g (n = 31). Experimental DesignNorepinephrine dose response of adipose tissue lipolysis in vitro was studied in 12 control and 12 diabetic rats. Animals were killed and epididymal fat pads were immediately removed and placed into incubation medium, which was Krebs-Ringer...