Journal of Lipid Research, Vol. 20, 848-856, September 1979
Copyright © 1979 by Lipid Research, Inc.

Insulin insensitivity and altered glucose utilization in cultured rat adipose tissue

Robert S. Bernstein

Medical Service, St. Luke's Hospital Center, New York, NY 10025 and Department of Medicine and Institute of Human Nutrition, Columbia University, College of Physicians & Surgeons

Glucose utilization was studied in isolated fat cells prepared from rat adipose tissue which had been cultured for 18 hr in TC 199 medium. When 1% bovine serum albumin (BSA) was in the culture medium, basal rates of ¹⁴CO₂ and [¹⁴C]triglyceride production from [1-¹⁴C]glucose were markedly depressed and there was no effect of insulin. With 4% BSA, basal ¹⁴CO₂ production was the same as in cells prepared from fresh tissue and basal triglyceride production was greatly increased. Insulin effect on these cells was minimal. One-minute uptake of [¹⁴C]2-deoxyglucose was stimulated by 800-1000% in fresh cells and 300-500% in cells cultured with either 1% or 4% BSA. Oxidation of [U-¹⁴C]glucose showed a much smaller impairment in cultured cells than for [1-¹⁴C]glucose, suggesting that the pentose phosphate shunt was more severely impaired than glycolysis. Glyceride-glycerol production was increased in cultured cells relative to preculture (fresh) cells. There was no effect of insulin in the culture medium in any of these systems. Rates of free fatty acid and glycerol release were markedly increased in cultured cells, especially when insulin was present in the culture medium. The acute antilipolytic effect of insulin was retained, so that insulin in the test incubation decreased lipolysis by 40-80%. Nevertheless, cell-associated fatty acids were increased in cultured cells and FFA/albumin ratios in the medium often reached potentially toxic levels. The reduction in pentose phosphate shunt activity, lipogenesis, and insulin effect resembles other models of insulin insensitivity. The impaired metabolism is probably due to an intracellular defect. A possible toxic role of either intracellular or extracellular fatty acids cannot be excluded. This system should be a useful model in which to study the cellular mechanisms of insulin insensitivity in adipocytes.—Bernstein, R. S. Insulin insensitivity and altered glucose utilization in cultured rat adipose tissue.

Supplementary key words 2-deoxyglucose • pentose phosphate shunt • lipogenesis

Submitted on February 5, 1979
Accepted on May 4, 1979

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