Insulin sensitivity is increased in Friend erythroleukemia cells enriched in polyunsaturated fatty acid

B H Ginsberg; P Chatterjee; M A Yorek

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Journal article

Insulin sensitivity is increased in Friend erythroleukemia cells enriched in polyunsaturated fatty acid

B H Ginsberg, P Chatterjee and M A Yorek

Receptor, Vol.1(3), pp.155-166

1991

PMID: 1843205

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Abstract

Increases in membrane lipid unsaturation and drug-induced increases in membrane fluidity have been shown to be associated with increases in insulin receptor concentration in animals, cultured cells, and liposomes. In the current study, we have examined the effect of increased membrane fatty acid unsaturation on insulin action. Friend Erythroleukemia cells were grown with exogenous polyunsaturated fatty acids for three days. After growth in medium supplemented with fatty acids, the unsaturation index of the phospholipids increased from 1.08 to 1.92, and this was associated with a significant decrease in anisotropy, as measured by fluorescence polarization. When measured at 15 degrees C, insulin receptor number rose from 9000 to 22,000 per cell with increased fatty acid unsaturation. The affinity for insulin in the polyunsaturated fatty acid treated cells decreased, however, resulting in similar amounts of insulin binding at low insulin concentrations but more binding at high insulin concentrations when compared to control cells. In contrast, binding of IGF-I was not influenced by increased membrane fatty acid unsaturation. When measured at 37 degrees C there were no changes in binding of insulin or IGF-I. Internalization of insulin was identical in control cells and in cells with increased membrane fatty acid unsaturation. Thymidine incorporation, an insulin-dependent function in these cell, was measured in control and fatty acid treated cells. In control cells, insulin increased thymidine incorporation by 80%, with an ED50 of about 5 nM. In cells treated with polyunsaturated fatty acids, the insulin stimulated thymidine incorporation was slightly higher and the ED50 was about 0.2 nM. In contrast, there was no increase in the sensitivity or responsiveness of fatty acid treated cells to IGF-I. We conclude that increased membrane fatty acid unsaturation greatly influences insulin binding and biological sensitivity, but not that of IGF-I. At low insulin levels, there was a greater insulin bioeffectiveness, despite the same or lower insulin binding, suggesting more efficient coupling of the insulin-effector complex.

Receptor, IGF Type 1 - metabolism

Leukemia, Erythroblastic, Acute - metabolism

Fatty Acids, Unsaturated - metabolism

Membrane Lipids - chemistry

Cell Division - physiology

Cell Membrane - chemistry

Insulin - metabolism

Animals

Sensitivity and Specificity

Friend murine leukemia virus

Membrane Lipids - metabolism

Tumor Cells, Cultured

Fluorescence Polarization

Insulin-Like Growth Factor I - metabolism

Details

Title: Subtitle: Insulin sensitivity is increased in Friend erythroleukemia cells enriched in polyunsaturated fatty acid
Creators: B H Ginsberg - Veterans Administration Medical Center, Iowa City, IA
P Chatterjee
M A Yorek
Resource Type: Journal article
Publication Details: Receptor, Vol.1(3), pp.155-166
PMID: 1843205
NLM abbreviation: Receptor
ISSN: 1052-8040
Grant note: AM 25295 / NIADDK NIH HHS
Language: English
Date published: 1991
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094613702771

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