Abstract
Leptin is a hormone that stimulates glucose uptake in some peripheral tissues and enhances whole-body insulin sensitivity through the sympathetic nervous system. However, the molecular mechanism remains to be elucidated. In the present study, we investigated how leptin and melanocortin receptor agonist (MT II) increase glucose uptake in peripheral tissues in mice. Microinjection of leptin into the ventromedial hypothalamus increased glucose uptake in skeletal muscle (SM) and brown adipose tissue (BAT). Intracerebroventricular injection of MT II also increased glucose uptake and serine phosphorylation of Akt in SM and BAT. When MT II was injected intracerebroventricularly and insulin is administered intravenously maintaining plasma glucose level, the glucose uptake by SM increased beyond the value in response to insulin stimulation alone. In mouse myoblastoma C2C12 cell, β-adrenergic receptor agonist (β-ARA) stimulated tyrosine phosphorylation of IRS1 without significant change in tyrosine phosphorylation of insulin receptor β subunit. β-ARA enhanced insulin-induced tyrosine phosphorylation of IRS1 and serine phosphorylation of Akt. β-ARA phosphorylated Src, which may act as IRS1-tyrosine kinase. In conclusion, our data suggest that hypothalamic leptin-melanocortin-β-adrenergic system increases glucose uptake and insulin sensitivity in SM and BAT. Glucose uptake in SM appears to be associated with the enhancement of insulin signaling. Src kinase is a putative mediator for the enhancement of insulin signaling in response to β-adrenergic stimulation. [J Physiol Sci. 2008;58 Suppl:S104]
