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 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.

Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men

“…There are several studies in which IGFBP-1 was shown to be a marker of hyperinsulinaemia [1,32,33]. As expected, fasting IGFBP-1 concentrations correlated inversely with fasting insulin levels in our study.…”

“…IGFBP-1 synthesis is regulated by insulin and other factors that are altered in conditions associated with abnormal glucose regulation. The suppression of IGFBP-1 production by insulin is achieved within the physiological range of insulin concentrations [1][2][3]. There are multiple stimulators, including glucagon [4] and inflammatory cytokines [5,6].…”

Effects of early gestation GH administration on placental and fetal development in sheep

“…The decrease in caruncle expression of IGFBP-1 can be attributed to two possible mechanisms. First, IGFBP-1 is inversely regulated by insulin (Suikkari et al 1989), and it has been shown previously that GH administration during gestation leads to hyperinsulinemia (Wallace et al 2004). Given that we achieved significant stimulation of IGF-I similar to that reported by Wallace et al one could reason that we generated a similar insulin response that reduced caruncle expression of IGFBP-1.…”

Impaired glucose homeostasis in insulin-like growth factor binding protein-1 transgenic mice.

“…Thus, the turnover of IGF present in the ternary complex is relatively slow (7). In contrast to IGFBP-3, the levels of IGFBP-1 vary considerably throughout the day and are inversely regulated by insulin (5,11,21,22). The unique pattern of regulation of IGFBP-1 expression suggests that this binding protein may have some role in modulating the free component of IGF-I and thus may be important in blood glucose control (5).…”