Scientists have identified a link between two major pathways that regulate blood glucose levels, as published online by Nature. One stimulates glucose production in the liver during fasting; the other causes the liver to inhibit glucose production under stressful conditions and during exercise.
Marc Montminy and colleagues found that both pathways act in an opposing way on a common target - a protein called TORC2 that helps to switch on genes that lead to glucose production in the liver. TORC2 must enter the nucleus in order to act, and it turns out that the two pathways regulate the activity of TORC2 by controlling its movement into the nucleus. Fasting conditions cause a phosphate molecule to be removed from TORC2, which allows it to enter the nucleus and switch on gluconeogenic genes. Under conditions of stress and energy deprivation, TORC2 becomes phosphorylated and can't enter the nucleus, so its function is inhibited.
The finding might eventually lead to therapeutic ways to enhance TORC2 phosphorylation to inhibit glucose formation in the liver, a process that is excessively activated in people with type 2 diabetes, the authors say.
Marc Montminy (Salk Institute for Biological Studies, La Jolla, CA, USA)
Abstract available online.
(C) Nature press release.
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