Regulation of lipoprotein lipase by glucose in primary cultures of isolated human adipocytes. Relevance to hypertriglyceridemia of diabetes

P. A. Kern, A. Mandic, R. H. Eckel

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15 Scopus citations

Abstract

Human adipose tissue lipoprotein lipase (LPL) is stimulated in vivo by an insulin-glucose infusion. However, previous work by us showed no effect of physiologic insulin concentrations of LPL in isolated human adipocytes. To pursue further the regulation of LPL in vitro, primary cultures of isolated human adipocytes were prepared and exposed to glucose concentrations of 0-4.5 mg/ml. LPL activity was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests (EXT). After 5 h in culture, a stimulatory effect of glucose on HR was observed. After 24 h there was a gradual increase in CM, HR, and EXT in parallel with increasing glucose concentrations of 0-1.0 mg/ml. At glucose concentrations >1.0 mg/ml, however, there was a decrease in CM. At a glucose concentration of 4.5 mg/ml, CM was only 51 ± 14% (P<.02) of its value at glucose concentrations of 1.0 mg/ml. Cellular LPL (HR and EXT) was not affected by high glucose concentrations. Response of cellular LPL to the hormonal regulator insulin-like growth factor I (IGF-I) was modulated by medium glucose. HR in cultures treated with 50 ng/ml IGF-I was 166 ± 40 and 147 ± 23% of HR in control cultures at glucose concentrations of 1.0 and 2.5 mg/ml, respectively (P≤.05). However, IGF-I failed to stimulate HR at glucose concentrations >2.5 mg/ml or <1.0 mg/ml. Adipocyte protein synthetic rate was not inhibited by medium containing 4.5 mg/ml glucose, suggesting that these high glucose concentrations were not generally toxic to cells. The hexoses galactose, L-glucose, and 3-O-methylglucose had no effect on LPL, but pyruvate and D-glucose stimulated HR. Cellular ATP was relatively constant regardless of medium conditions and bore no relationship to LPL. Thus, glucose plays an important role in the regulation of LPL in isolated human adipocytes. In addition, the decrease in CM and the blunted response of HR to IGF-I in high glucose suggest that hyperglycemia per se may contribute to the decreased LPL and consequent hypertriglyceridemia of poorly controlled diabetes.

Original languageEnglish
Pages (from-to)1238-1245
Number of pages8
JournalDiabetes
Volume36
Issue number11
DOIs
StatePublished - 1987

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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