Epinephrine-dependent control of glucose metabolism in white adipose tissue: the role of α- and β-adrenergic signalling.

Epinephrine controls many important and sometimes opposite processes. This pleiotropic effect is achieved via coupling to different receptor/effector systems. In epididymal white adipose tissue (EWAT) of Wistar rats, we showed that epinephrine stimulated protein kinase B (PKB) phosphorylation on Ser(473). Epinephrine further increased the glucose incorporation into glyceride-glycerol without decreasing glucose availability for other metabolic pathways (i.e. lactate production). Wortmannin (phosphatidylinositol 3-kinase inhibitor) treatment significantly decreased glucose incorporation into glyceride-glycerol and elevated the epinephrine-induced release of free fatty acids (FFA) from the adipose tissue without any change in the intensity of lipolysis measured as glycerol release. Using specific cyclic adenosine monophosphate (cAMP) analogs we demonstrated that cAMP-protein kinase A signalling resulted in a strong PKB dephosphorylation and significantly lowered the glucose availability in EWAT. Specific activation of the Epac (exchange protein activated by cAMP)-dependent pathway had only a moderately negative effect on PKB phosphorylation and glucose metabolism. In contrast, α(1) agonist methoxamine increased PKB phosphorylation and lactate production. This effect of methoxamine was additive to the effect of insulin and it was abolished by wortmannin treatment. In EWAT of spontaneously dyslipidemic hereditary hypertriglyceridemic (HHTg) rats, we demonstrated significantly lower epinephrine-induced glucose utilization but higher sensitivity to its lipolytic effect. We conclude that in EWAT, epinephrine controls two opposite processes (FFA release and FFA retention) via two different effector systems. The impairment of α(1)-dependent, epinephrine-stimulated, glycolysis-dependent FFA esterification may contribute to the establishment of dyslipidemia in insulin resistance.

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