Dose-response characteristics for suppression of low molecular weight plasma insulin-like growth factor-binding protein by insulin.
We previously demonstrated that supraphysiological insulin concentrations reduced the plasma 34K insulin-like growth factor-binding protein (IGF-BP) concentrations in humans. In this study we examined whether physiological changes in plasma insulin concentrations regulate IGF-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 in 23 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 less than 0.0001). In the caucasian group the mean plasma IGF-BP concentration was higher [15 +/- 4 (+/- SE) micrograms/L] than in the Indian group (8 +/- 2 micrograms/L; P less than 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 less than 0.001). After oral glucose 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 half-maximal 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.
Suikkari
A M
AM
First Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland.
Koivisto
V A
VA
Koistinen
R
R
Seppälä
M
M
Yki-Järvinen
H
H
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000097:blood / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005455:Fluorescent Antibody Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D018969:Insulin-Like Growth Factor Binding Proteins; D008297:Male; D008970:Molecular Weight; D013002:Somatomedins / Q000502:physiology*
D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins