Print Email Facebook Twitter Dynamics of insulin signalling in liver during hyperinsulinemic euglycaemic clamp conditions in vivo and the effects of high-fat feeding in male mice Title Dynamics of insulin signalling in liver during hyperinsulinemic euglycaemic clamp conditions in vivo and the effects of high-fat feeding in male mice Author Korsheninnikova, E. Voshol, P.J. Baan, B. van der Zon, G.C.M. Havekes, L.M. Romijn, J.A. Maassen, J.A. Ouwens, D.M. TNO Kwaliteit van Leven Publication year 2007 Abstract Insulin is an important regulator of hepatic carbohydrate, lipid, and protein metabolism, and the regulation of these processes by insulin is disturbed under conditions of insulin resistance and type 2 diabetes. Despite these alterations, the impact of insulin resistance on insulin signalling in the liver is not well defined. Variations in time and dose of insulin stimulation as well as plasma glucose levels may underlie this. The present study aimed at determining the dynamics of activation of hepatic insulin signalling in vivo at insulin concentrations resembling those achieved after a meal, and addressing the effects of high-fat feeding. An unexpected finding of this study was the biphasic activation pattern of the IRS-PI3K-PKB/Akt pathway. Our findings indicate that the first burst of activation contributes to regulation of glucose metabolism. The physiological function of the second peak is still unknown, but may involve regulation of protein synthesis. Finally, high-fat feeding caused hepatic insulin resistance, as illustrated by a reduced suppression of hepatic glucose production. A sustained increased phosphorylation of the serine/threonine kinases p70S6kinase and Jun N-terminal kinase in the absence of insulin may underlie the abrogated phosphorylation of the IRS proteins and their downstream targets. Subject BiologyBiomedical ResearchHepatic glucose productionHigh-fat dietInsulin resistanceInsulin signallingLiverglucoseinsulininsulin receptorphosphatidylinositol 3 kinaseprotein kinase BanimalarticlebloodC57BL mousedrug effectfat intakegene expression regulationglucose clamp techniquehyperinsulinismlivermalemetabolismmousesignal transduction1-Phosphatidylinositol 3-KinaseAnimalsDietary FatsGene Expression Regulation, EnzymologicGlucoseGlucose Clamp TechniqueHyperinsulinismInsulinLiverMaleMiceMice, Inbred C57BLProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionMus To reference this document use: http://resolver.tudelft.nl/uuid:4898e6cd-dae3-491a-9645-ccf7d21c8550 DOI https://doi.org/10.1080/13813450701669084 TNO identifier 240235 ISSN 1381-3455 Source Archives of Physiology and Biochemistry, 113 (4-5), 173-185 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.