Dose-Response Characteristics for Suppression of Low Molecular Weight Plasma Insulin-Like Growth Factor-Binding Protein by Insulin*

Abstract

We previously demonstrated that supraphysiological insulin concentrations reducedthe plasma 34K insulinlike growth factor-binding protein (IGF-BP) concentrations in humans. Inthis study we examined whether physiological changes in plasma insulin concentrations regulateIGF-BP and, if so, whether the regulation is influenced by race, glucose tolerance, or rate of glucose metabolism. For these purposes we 1) analyzed the relationship between fasting plasma insulin and IGF-BP concentrations in 2 racial groups (23 Caucasians and 35 southwestern American Indians), 2) measured the response of plasma IGF-BP to oral glucose in 20 normal subjects, and 3) determined the dose-response characteristics of plasma IGF-BP to glucose and insulin in23 normal subjects at 4 different insulin and glucose concentrations. The fasting plasma insulin concentration was inversely related to the plasma IGF-BP concentration in both the Caucasian and Indian groups (P < 0.0001). In the Caucasian group the mean plasma IGF-BP concentrationwas higher [15 ± 4 (±se) μg/L] than in the Indian group (8 ± 2 μg/L; P < 0.05). This difference was independent of race and glucose tolerance, and it could be explained by lower plasma insulin concentrations in the Caucasian (387 ± 50 pmol/L) than in the Indian group (215 ± 43 pmol/L; P < 0.001). After oralglucose administration, the insulin concentration (423 ± 72 pmol/L) was maximal 30 min after glucose treatment, and significant suppression of the IGF-BP concentration occurred at 90 min. Analysis of the dose-response curves revealed maximal suppression of IGF-BP at about 1150 pmol/L insulin, and halfmaximal suppression at about 290 pmol/L. The plasma glucose concentration or the rate of glucose metabolism had no effect on the IGF-BP concentration. These data suggest that insulin is a major regulator of plasma IGF-BP concentrations under physiological conditions.