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

First Department of Obstetrics and Gynecology, University Central Hospital (A.-M.S., R.K., M.S.) Haartmaninkatu 2
The Second Department of Medicine, University Central Hospital (V.A.K.) Helsinki, Finland
The Clinical Diabetes and Nutrition Section, National Institute of Diabetes, Digestive Diseases and Kidney Diseases, National Institutes of Health (H. Y.-J.) Phoenix, Arizona 85016

Address all correspondence and requests for reprints to: Dr. Anne- Maria Suikkari, Department I of Obstetrics and Gynecology, University Central Hospital, Haartmaninkatu 2, SF-00290 Helsinki, Finland.

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.

^* This work was supported by grants from the Finnish Cancer Research Foundation, the Academy of Finland, and the Sigrid Juselius Foundation.

Received April 7, 1988.

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