Hepatic gluconeogenesis is critical to glucose homeostasis. It contributes to hyperglycemia in type 2 diabetes when the function is too strong. It causes hypoglycemia in fasting condition if the function is too weak. Regulation of hepatic gluconeogenesis is an hot area and many transcription factors and cofactors have been identified in the mechanism study, such as FOXO1, GR, CREB, HNF4, PGC-1, and SIRT1. In the current issue of Nature Medicine, a new study suggests that ligand-independent nuclear receptors (Nur77, Nurr1 and NOR1) are involved in hepatic gluconeogenesis in the response to glucogan-cAMP pathway. Expression of these receptors are induced by cAMP-CREB axis. Attached is the PDF file of the paper.

Insulin receptor contains two alpha subunits and two beta subunits. The alpha subunits bind to insulin and the beta units catalyze tyrosine phosphorylation of itself and the IRS proteins. It was not clear how the receptor forms the binding site for insulin. In the current issue of Nature, this question is addressed by a study using protein crystal structure. See attached paper.

Gluconeogenesis and NR4A 

Structure of insulin receptor

by Jianping at PBRC/LSU
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Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225) 763-3163
Fax: (225) 763-2525
E-mail: yej@pbrc.edu