Production of insulin resistance by hyperinsulinaemia in man

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

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220 Scopus citations

Abstract

It has been proposed that hyperinsulinaemia may cause or exacerbate insulin resistance. The present studies were undertaken to test this hypothesis in man. Glucose utilization, glucose production, and overall glucose metabolism at submaximally and maximally effective plasma insulin concentrations (∼80 and ∼1700 mU/l), and monocyte and adipocyte insulin binding were measured in normal volunteers on two occasions: once after 40 h of hyperinsulinaemia (25-35 mU/l) produced by infusion of insulin and once after infusion of saline (75 mmol/l; plasma insulin ∼10 mU/l). After 40 h of hyperinsulinaemia, glucose utilization and overall glucose metabolism at submaximally and maximally effective plasma insulin concentrations were both slightly, but significantly, reduced compared with values observed after the infusion of saline (p<0.05), whereas glucose production rates were unaffected. Monocyte and adipocyte binding were also unaffected. These results indicate that hyperinsulinaemia of the magnitude observed in insulin resistant states, such as obesity, can produce insulin resistance in man. Assuming that human insulin sensitive tissues possess spare insulin receptors and that monocyte and adipocyte insulin binding accurately reflect insulin binding in insulin-sensitive tissues, the decreased maximal responses to insulin and the lack of change in insulin binding suggest that this insulin resistance occurred at a post-binding site.

Original languageEnglish (US)
Pages (from-to)70-75
Number of pages6
JournalDiabetologia
Volume28
Issue number2
DOIs
StatePublished - Feb 1 1985

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Keywords

  • Hyperinsulinaemia
  • glucose utilization
  • insulin resistance

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Rizza, R. A., Mandarino, L. J., Genest, J., Baker, B. A., & Gerich, J. E. (1985). Production of insulin resistance by hyperinsulinaemia in man. Diabetologia, 28(2), 70-75. https://doi.org/10.1007/BF00279918