Regulation of hepatic glucose metabolism in health and disease
By Max C. Petersen, D. Vatner, Gerald I. Shulman. Nature Reviews Endocrinology, 2017
995 citations recorded by the source corpus.
The liver is crucial for the maintenance of normal glucose homeostasis — it produces glucose during fasting and stores glucose postprandially. However, these hepatic processes are dysregulated in type 1 and type 2 diabetes mellitus, and this imbalance contributes to hyperglycaemia in the fasted and postprandial states. Net hepatic glucose production is the summation of glucose fluxes from gluconeogenesis, glycogenolysis, glycogen synthesis, glycolysis and other pathways. In this Review, we discuss the in vivo regulation of these hepatic glucose fluxes. In particular, we highlight the importance of indirect (extrahepatic) control of hepatic gluconeogenesis and direct (hepatic) control of hepatic glycogen metabolism. We also propose a mechanism for the progression of subclinical hepatic insulin resistance to overt fasting hyperglycaemia in type 2 diabetes mellitus. Insights into the control of hepatic gluconeogenesis by metformin and insulin and into the role of lipid-induced hepatic insulin resistance in modifying gluconeogenic and net hepatic glycogen synthetic flux are also discussed. Finally, we consider the therapeutic potential of strategies that target hepatosteatosis, hyperglucagonaemia and adipose lipolysis.
Subfields: Endocrinology, Diabetes and Metabolism, Molecular Biology, Surgery
View Paper: https://www.semanticscholar.org/paper/9bcce574867f32a95c3420491e96ca75ebd2f96e
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Citations in the corpus
- Trends in insulin resistance: insights into mechanisms and therapeutic strategy (2022, background): “Despite stimulated glucose uptake, insulin rapidly reduces hepatic glucose output and hepatic glucose production (HGP) by activating glycogen synthesis, and suppressing glycogenolysis and gluconeogenesis in liver.(107,108) Further, gluconeogenesis suppression by insulin is mediated by inhibition of ”
- Cellular and Molecular Mechanisms of Metformin Action (2020, background): “The CREB–CREB-binding protein (CBP)–CREB-regulated transcription co-activator 2 (CRTC2) transcriptional complex increases expression of glucose-6-phosphatase ( G6pc ) and phosphoenolpyruvate carboxykinase 1 ( Pck1 ), 2 gluconeogenic genes (91, 92).”