Direct evidence for downregulation of insulin receptors by physiologic hyperinsulinemia in man

V. R. Soman, R. A. DeFronzo

Resultado de la investigación: Comment/debaterevisión exhaustiva

5 Citas (Scopus)


To directly examine whether physiologic hyperinsulinemia regulates insulin receptors in normal man, we studied the effect of insulin infusion (employing the euglycemic insulin clamp technique) on 125I-insulin binding to monocytes. In Study I (9 subjects), when the steady-state plasma insulin concentration was raised to approximately 100 μU/ml, insulin binding to monocytes remained unchanged at 1 h, but decreased significantly by 3 h (20%, P<0.01) and fell further by 5 h (37%, P<0.001) following the insulin infusion. In Study II (5 subjects) increments in plasma insulin concentration to 31 μU/ml resulted in no change in insulin binding at 3 h (P>0.5) but resulted in a significant decrease at 5 h (25%, P<0.01). The plasma glucose concentration was maintained at basal levels in both infusion protocols. The decrease in insulin binding in both studies was due to a decrease in insulin receptor concentration. No significant change in receptor affinity was observed. In a control study (5 subjects) 5 h of saline infusion had no effect on insulin binding to monocytes. We conclude that in normal humans, increments in the plasma insulin concentration in the physiologic range downregulates the number of insulin receptors in a dose- and time-dependent manner.

Idioma originalEnglish (US)
Páginas (desde-hasta)159-163
Número de páginas5
EstadoPublished - 1980
Publicado de forma externa

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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