Glucose homeostasis is regulated by hormones and cellular energy status. Elevations of blood glucose during feeding stimulate insulin release from pancreatic beta-cells through a glucose sensing pathway. Feeding also stimulates release of gut hormones such as glucagon-like peptide-1 (GLP-1), which further induces insulin release, inhibits glucagon release and promotes beta-cell viability. CREB-dependent transcription likely plays a role in both glucose sensing and GLP-1 signaling . The protein Torc2 (transducer of regulated CREB activity 2) functions as a CREB co-activator and is implicated in mediating the effects of these two pathways . In quiescent cells, Torc2 is phosphorylated at Ser171 and becomes sequestered in the cytoplasm via an interaction with 14-3-3 proteins. Glucose and gut hormones lead to the dephosphorylation of Torc2 and its dissociation from 14-3-3 proteins. Dephosphorylated Torc2 enters the nucleus to promote CREB-dependent transcription. Torc2 plays a key role in the regulation of hepatic gluconeogenic gene transcription in response to hormonal and energy signals during fasting.Tissue specificity: Most abundantly expressed in the thymus. Present in both B and T lymphocytes. Highly expressed in HEK293T cells and in insulinomas. High levels also in spleen, ovary, muscle and lung, with highest levels in muscle. Lower levels found in brain, colon, heart, kidney, prostate, small intestine and stomach. Weak expression in liver and pancreas .
