Editors' ChoiceCell Signaling

Directly Modulating Glucose Homeostasis

Science Signaling  11 Mar 2008:
Vol. 1, Issue 10, pp. ec93
DOI: 10.1126/stke.110ec93

The concentration of glucose in the bloodstream is regulated by glucose itself, along with the hormones insulin and glucagon. Glucagon stimulates gluconeogenesis in part by regulating phosphorylation of a transcriptional coactivator known as cyclic adenosine monophosphate response element-binding protein 2 (CRTC2). Dentin et al. (see the Perspective by Birnbaum) found that high concentrations of circulating glucose also regulate CRTC2, but do so through stimulation of the hexosamine biosynthetic pathway and consequent O-linked glycosylation of the same serine residue in CRTC2 that is modified by phosphorylation. Thus, CRTC2 integrates signals from hormones and nutrients and might be a target for efforts to treat abnormalities of glucose homeostasis that are associated with diabetes.

R. Dentin, S. Hedrick, J. Xie, J. Yates, III, M. Montminy, Hepatic glucose sensing via the CREB coactivator CRTC2. Science 319, 1402-1405 (2008). [Abstract] [Full Text]

M. J. Birnbaum, Sweet conundrum. Science 319, 1348-1349 (2008). [Summary] [Full Text]