Infusion of insulin impairs human adipocyte glucose metabolism in vitro without decreasing adipocyte insulin receptor binding

L. Mandarino, B. Baker, R. Rizza, J. Genest, J. Gerich

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

To determine whether hyperinsulinaemia can cause insulin resistance in man and, if so, whether this occurs at a receptor or post-receptor site, nine normal volunteers were infused with insulin for 6 h at a rate (2 mU·kg-1·min-1) which resulted in steady-state plasma insulin concentrations of 140±13mU/l and four subjects were infused with saline (0.45%). Isolated adipocytes and monocytes were used as models for studying insulin binding, while adipocytes were also used to study insulin action in vitro. Adipocyte insulin binding did not decrease following infusion of insulin (4.6±0.5 versus 4.4±0.4% per 2×105 cells, before and after, respectively), whereas monocyte insulin binding did (7.2±0.6 versus 6.2±0.6% per 107 cells, p<0.05). Initial rates of adipocyte 3-0-methyl glucose transport were decreased in the absence of insulin (basal) and at submaximally effective (33.3pmol/l) but not at maximally effective insulin concentrations. At all insulin concentrations and in the absence of insulin, rates of glucose conversion to lipids were decreased more than 50% (p<0.05), whereas rates of glucose oxidation were unaffected. This decrease in the rates of conversion of glucose to lipids could not be accounted for by the decrease in rates of glucose transport. These results suggest that hyperinsulinaemia can cause insulin resistance in man and that, at least initially, this occurs at a post-receptor site. Furthermore, the discordant effect of hyperinsulinaemia on monocyte and adipocyte insulin binding indicates that monocyte insulin binding may not always reflect insulin binding in insulin-sensitive tissues.

Original languageEnglish (US)
Pages (from-to)358-363
Number of pages6
JournalDiabetologia
Volume27
Issue number3
DOIs
StatePublished - Sep 1984

Keywords

  • Hyperinsulinaemia
  • adipocytes
  • insulin resistance
  • receptors

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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