title: Control of hepatic glucose metabolism by islet and brain.
abstract: Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP) contribute to hyperglycaemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver but also through a mechanism involving the brain. Yet, the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice, investigating whether the direct hepatic action of insulin is necessary for normal HGP: when the hepatic insulin signalling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here, we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients.
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Rojas
authors.forename: M W
authors.initials: MW
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D025461:Feedback, Physiological; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000819:agonists / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000294:innervation / Q000378:metabolism*; D008099:Liver / Q000294:innervation / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D005947:Glucose
keywords: hepatic glucose production; hepatic glucose uptake; hypothalamus; obesity; pancreas; type 2 diabetes