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
Biology
Biomedical Research
Hepatic glucose production
High-fat diet
Insulin resistance
Insulin signalling
Liver
glucose
insulin
insulin receptor
phosphatidylinositol 3 kinase
protein kinase B
animal
article
blood
C57BL mouse
drug effect
fat intake
gene expression regulation
glucose clamp technique
hyperinsulinism
liver
male
metabolism
mouse
signal transduction
1-Phosphatidylinositol 3-Kinase
Animals
Dietary Fats
Gene Expression Regulation, Enzymologic
Glucose
Glucose Clamp Technique
Hyperinsulinism
Insulin
Liver
Male
Mice
Mice, Inbred C57BL
Proto-Oncogene Proteins c-akt
Receptor, Insulin
Signal Transduction
Mus
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