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Effects of free fatty acids on 2-deoxyglucose uptake in human fibroblasts

Free fatty acid (FFA) levels in obese humans are known to be inversely correlated with insulin-stimulated glucose uptake. To test similar interaction in human dermal fibroblasts, a mixture of FFA at approximately the molar ratios found in human serum was added to incubation medium (Dulbecco's MEM with 1 g/l glucose and 10% fetal calf serum), using bovine serum albumin (BSA) as a carrier. Control dishes had BSA and added glucose to make dishes isocaloric. Cells were grown for 5-l4 days (7 was standard). Tritiated 2-deoxy-D-glucose (2DG) uptake from glucose-free buffer was monitored after preincubation with or without maximally stimulating insulin for 1 hour. Uptake rates increased with longer growth as glucose was metabolized, an apparent starvation effect. Addition of FFA did not significantly change non-insulin stimulated (basal) 2DG uptake compared to isocaloric control. Insulin-stimulated uptake was reduced by increasing levels of FFA. Multiple polynomial regression showed significant interaction of insulin and FFA. Addition of extra calories as FFA decreased both basal and insulin-stiumlated uptake, possibly a glucose-sparing effect when metabolic glucose disappearance was less rapid. Chronic exposure of cells to FFA reduces insulin-stimulated glucose uptake compared to isocaloric control in human fibroblasts, as seen in perfused tissues and whole animals. FFA may also reduce basal glucose uptake beyond the effect expected from the sparing of medium glucose.

Identiferoai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:dissertations-7811
Date01 January 1990
CreatorsRosholt, Mary Nicolette
PublisherScholarWorks@UMass Amherst
Source SetsUniversity of Massachusetts, Amherst
LanguageEnglish
Detected LanguageEnglish
Typetext
SourceDoctoral Dissertations Available from Proquest

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