Expression of α2-Receptor-Mediated Responses by Insulin in Primary Culture of Rat Hepatocytes

[摘要] References(20)Cited-By(3)The effects of the α2-adrenergic agonist, clonidine, on the glucagon-stimulated glucose output from serum-free cultures of adult rat hepatocytes were examined in vitro. When hepatocytes were cultured with 10 nM dexamethasone under the serum-free condition, 1 or 10 μM clonidine did not inhibit the glucagon-induced glucose production. In contrast, clonidine dose-dependently inhibited the activity concomitantly with suppression of hepatocyte cAMP production by glucagon when they were cultured with 10 nM dexamethasone and 10 nM insulin. The inhibitory effects of clonidine were completely blocked by prior treatment of hepatocytes with pertussis toxin (100 ng/ml). In addition, forskolin-stimulated cAMP production was also inhibited by α2-adrenergic agonists (clonidine and oxymetazoline) in a dose-dependent manner when hepatocytes were cultured with 10 nM dexamethasone and 10 nM insulin. The inhibitory effects of α2-adrenergic agonists on forskolin-stimulated cAMP production were specifically blocked when they were combined with the α2-adrenergic antagonist yohimbine. Hepatocytes cultured with dexamethasone alone showed no response to the α2-adrenergic agonists. The α2-response was abolished when cycloheximide (0.5 μM) was added to the cultures. These results suggest that insulin develops α2-adrenergic responsiveness through new protein synthesis during the primary culture of adult rat hepatocytes.

[学科分类] 药理学

[关键词] Hepatic glucose output;cAMP production;Insulin;α2-Adrenergic agonist