Mechanism of norepinephrine stimulation of glucose transport in isolated rat brown adipocytes.

Cold exposure reverses the diabetogenic effects of high-fat feeding and markedly stimulates glucose uptake in rat brown adipose tissue (BAT). Considering that cold exposure increases the plasma levels of norepinephrine and lipolytic hormones, but decreases the levels of insulin, we have examined the effects of these agents on glucose transport in isolated rat brown adipocytes using D-[U-14C]glucose as a tracer. It was found that norepinephrine (0.1 microM), glucagon (0.1 nM) and ACTH (100 nM) all increased brown adipocyte respiration (2-10 times) and glucose transport (2-5 times). Studies with adrenergic agonists and antagonists revealed that norepinephrine increases glucose uptake via beta-adrenergic pathways. On the other hand, insulin also increased glucose transport (6 times) but inhibited (40-60 percent) the calorigenic effects of the lipolytic hormones. Both norepinephrine and glucagon potentiated the submaximal insulin responses for glucose transport, demonstrating the existence of metabolic interactions between norepinephrine-, glucagon-, and insulin-mediated glucose uptake. Remarkably, the stimulatory effects of these lipolytic agents were reproduced by dibutyryl cAMP (1 mM), isobutylmethylxanthine (0.1 mM) and palmitic acid (0.5 mM), suggesting that cAMP increases glucose transport via activation of lipolysis and thermogenesis. Considering that the stimulatory effects of norepinephrine (0.1 microM) on respiration and glucose transport were totally blocked by 2-tetradecylglycidic acid (50 microM), a specific inhibitor of mitochondrial carnitine acyl transferase, it is concluded that norepinephrine increases BAT glucose transport via fatty acid-activation of mitochondrial thermogenesis.