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Molecular signalling of fatty acids on glucokinase, hepatic glucose phosphorylation and glycolysis in the presence of insulin

Swagell, Christopher D., Morris, Charles P., & Henly, Debra C. (2006) Molecular signalling of fatty acids on glucokinase, hepatic glucose phosphorylation and glycolysis in the presence of insulin. Nutrition, 22(6), pp. 672-678.

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Abstract

Objective: There is evidence from in vitro studies that fatty acids can inhibit glucose uptake in liver. However, it is uncertain whether this happens in vivo when the liver is exposed to high levels of glucose and insulin, in combination with fatty acids, after a mixed meal. This study determined the effects of a combination of fatty acids and insulin on glucokinase (GK) activity and glycolysis in primary rat hepatocytes. Methods: Hepatocytes were cultured with 15 mM glucose and 2 or 10 nM insulin in combination with the fatty acids palmitate, oleate, linoleate, eicosapentaenoic acid, or docosahexaenoic acid. Total GK activity and the proportion of GK in the active, unbound state were measured to determine the effect of fatty acid on the activity and cellular localization of GK. Glucose phosphorylation and glycolysis were measured in intact cells. Lactate and pyruvate synthesis and the accumulation of ketone bodies were also estimated. Results: Palmitate and eicosapentaenoic acid lowered total GK activity in the presence of 2 nM insulin, but not with 10 nM insulin. In contrast, oleate, linoleate, and docosahexaenoic acid did not alter GK activity. None of the fatty acids tested inhibited glucose phosphorylation or glycolysis in intact rat hepatocytes. In addition, GK activity was unaffected by insulin concentration. Conclusion: Some fatty acids can act to inhibit GK activity in primary hepatocytes. However, there was no evidence that this decrease in GK activity impaired glucose phosphorylation or glycolysis. Glucose and high concentrations of insulin, which promote glucose uptake, appear to counteract any inhibitory action of fatty acids. Therefore, the presence of fatty acids in a normal mixed meal is likely to have little effect on the capacity of the liver to take up, phosphorylate, and oxidize glucose.

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7 citations in Web of Science®

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ID Code: 8863
Item Type: Journal Article
Additional Information: For more information, please refer to the journal's website (see hypertext link) or contact the author. Author contact details: p.morris@qut.edu.au
DOI: 10.1016/j.nut.2006.03.005
ISSN: 0899-9007
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cell Metabolism (060104)
Divisions: Current > Research Centres > CRC for Diagnostics
Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2006 Elsevier
Deposited On: 03 Aug 2007
Last Modified: 29 Feb 2012 23:30

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