Hypothalamic insulin signaling is required for inhibition of glucose production

S Obici, BB Zhang, G Karkanias, L Rossetti - Nature medicine, 2002 - nature.com
S Obici, BB Zhang, G Karkanias, L Rossetti
Nature medicine, 2002nature.com
Circulating insulin inhibits endogenous glucose production. Here we report that bidirectional
changes in hypothalamic insulin signaling affect glucose production. The infusion of either
insulin or a small-molecule insulin mimetic in the third cerebral ventricle suppressed glucose
production independent of circulating levels of insulin and of other glucoregulatory
hormones. Conversely, central antagonism of insulin signaling impaired the ability of
circulating insulin to inhibit glucose production. Finally, third-cerebral-ventricle …
Abstract
Circulating insulin inhibits endogenous glucose production. Here we report that bidirectional changes in hypothalamic insulin signaling affect glucose production. The infusion of either insulin or a small-molecule insulin mimetic in the third cerebral ventricle suppressed glucose production independent of circulating levels of insulin and of other glucoregulatory hormones. Conversely, central antagonism of insulin signaling impaired the ability of circulating insulin to inhibit glucose production. Finally, third-cerebral-ventricle administration of inhibitors of ATP-sensitive potassium channels, but not of antagonists of the central melanocortin receptors, also blunted the effect of hyperinsulinemia on glucose production. These results reveal a new site of action of insulin on glucose production and suggest that hypothalamic insulin resistance can contribute to hyperglycemia in type 2 diabetes mellitus.
nature.com