Regulation of lipoprotein lipase by glucose in primary cultures of isolated human adipocytes. Relevance to hypertriglyceridemia of diabetes.
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 on 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 greater than 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 less than .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 less than or equal to .05). However, IGF-I failed to stimulate HR at glucose concentrations greater than 2.5 mg/ml or less than 1.0 mg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Kern
P A
PA
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Mandic
A
A
Eckel
R H
RH
D000255:Adenosine Triphosphate / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000328:Adult; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000209:etiology* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008875:Middle Aged; D014176:Protein Biosynthesis; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D000255:Adenosine Triphosphate; D006493:Heparin; D008071:Lipoprotein Lipase; D005947:Glucose