Abstract:

Maintaining blood glucose concentration within a relatively narrow range through periods of fasting or excess nutrient availability is essential to the survival of the organism. This is achieved through an intricate balance between glucose uptake and endogenous glucose production to maintain constant glucose concentrations. The liver plays a major role in maintaining normal whole body glucose levels by regulating the processes of de novo glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis), thus controlling the levels of hepatic glucose release. Aberrant regulation of hepatic glucose production (HGP) can result in deleterious clinical outcomes, and excessive HGP is a major contributor to the hyperglycemia observed in Type 2 diabetes mellitus (T2DM). Indeed, adjusting glycemia as close as possible to a non-diabetic range is the foremost objective in the medical treatment of patients with T2DM and is currently achieved in the clinic primarily through suppression of HGP. Here, we review the molecular mechanisms controlling HGP in response to nutritional and hormonal signals and discuss how these signals are altered in T2DM.

Notes:

Sharabi, KfirTavares, Clint D JRines, Amy KPuigserver, PereengF32 DK102293/DK/NIDDK NIH HHS/F32DK102293-01/DK/NIDDK NIH HHS/R24 DK080261/DK/NIDDK NIH HHS/R01 DK081418/DK/NIDDK NIH HHS/R01 DK089883/DK/NIDDK NIH HHS/R01 DK069966/DK/NIDDK NIH HHS/R24 DK080261-06/DK/NIDDK NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tReviewEnglandMol Aspects Med. 2015 Dec;46:21-33. doi: 10.1016/j.mam.2015.09.003. Epub 2015 Nov 5.