Effect of prolonged hyperinsulinaemia on adipocyte insulin binding and action in normal man

Prolonged moderate insulinaemia over 20 h in normal humans produces a significant reduction of in vivo insulin action. To examine the effects in man of such moderate hyperinsulinaemia on in vitro glucose metabolism, insulin-receptor binding, glucose transport and incorporation of glucose into lipid were determined in adipocytes isolated from paired gluteal fat biopsies, taken from six normal human volunteers before and 1 h after 20 h of exogenous hyperinsulinaemia (plasma insulin 38 +/- 3 mU/l). Specific binding of insulin to isolated adipocytes was not altered (6.7 +/- 0.7 versus 7.6 +/- 1.5% per 10(5) cells). Basal glucose transport of 3-O-[14C]methylglucose in the absence of insulin was reduced after hyperinsulinaemia (5.2 +/- 1.1 versus post 4.3 +/- 1.3 pmol/7 s per 10(5) cells, 0.1 less than P greater than 0.05; or expressed as percent of maximal response: 60 +/- 5 versus post 49 +/- 1%, P less than 0.05), but maximal transport (9.2 +/- 1.5 versus post 8.7 +/- 1.5 pmol/7 s per 10(5) cells) and ED50 (87 +/- 17 versus 67 +/- 15 pmol/l) were unchanged. Conversion of glucose into lipid, using 3-D-[3H]glucose, was unchanged basally, at maximal response or ED50 of the dose response curve. In conclusion, moderate 20 h in vivo hyperinsulinaemia in normal humans induces only a small change in basal vitro adipocyte glucose transport, and no change in insulin-receptor binding or in vitro incorporation of glucose into lipid. These data suggest that the adipocyte does not contribute to the impaired insulin action produced by in vivo moderate hyperinsulinaemia in man.