Variables Controlling the Secretion of Insulin-Like Growth Factor Binding Protein-2 in Normal Human Subjects*

Abstract

Insulin-like growth factor binding protein-2 (IGFBP-2) is one of a family of IGFBPs that are present in extracellular fluids, and binds both IGF-II and IGF-I with high affinity. These studies were conducted to determine the nutritional and hormonal variables that regulate plasma IGFBP-2 concentrations in humans. The mean plasma IGFBP-2 concentration for 38 normal adult subjects was 150 +/- 61 micrograms/L and was 4.7-fold greater than their mean fasting IGFBP-1 value. Mean IGFBP-2 values in cord sera of 26 normal term infants was 3.8-fold greater than the normal adult mean value. Likewise, the mean value for 44 hypopituitary adults was increased 2-fold compared to normal. There was no suppression of IGFBP-2 values in acromegaly. Normal adult subjects showed minimal fluctuations (less than 2-fold changes) in plasma IGFBP-2 concentrations during a 48-h sampling period. These changes were significantly less than the changes that occurred in plasma IGFBP-1 during the same interval. Plasma IGFBP-2 did not change significantly post prandially or after a glucose infusion. Extreme insulin deficiency, after 9 days of fasting, was associated with a 1.7-fold increase in plasma IGFBP-2. Administration of GH, which is known to cause a major decrease in plasma IGFBP-1 and in IGFBP-2 in hypophysectomized animals, did not result in a change in calorically restricted normal adult subjects, suggesting that a normal caloric intake is required for GH to suppress IGFBP-2. In summary, these results show that plasma IGFBP-2 is regulated differently than IGFBP-1. Acute stimulation of insulin secretion does not suppress IGFBP-2, and there is much less daily fluctuation compared to IGFBP-1. These findings suggest that plasma IGFBP-2 levels are more stable than IGFBP-1, and therefore IGFBP-2 may serve as a larger reservior that is available for IGF transport.

Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone

“…34 Several reports have shown that IGFBP-2 is differentially regulated by GH and IGF-1. 12,34 Administration of GH causes a reduction in IGFBP-2, while the serum concentration of IGFBP-2 is high in states of GH de®ciency. 34 In normal adults, the infusion of IGF-1 results in suppression of GH and an increase in IGFBP-2.…”

“…12,34 Administration of GH causes a reduction in IGFBP-2, while the serum concentration of IGFBP-2 is high in states of GH de®ciency. 34 In normal adults, the infusion of IGF-1 results in suppression of GH and an increase in IGFBP-2. 38 The dissociation of the effect of GH and IGF-1 in regulating IGFBP-2 suggests that IGFBP-2 and the ratio of IGFBP-2 to IGF-1 may be useful in detecting GH de®ciency.…”

“…These ®nd-ings indicate that factors other than GH may be regulating serum IGFBP-2 in obesity. Clemmons et al 34 showed that acute stimulation of insulin did not suppress IGFBP-2, but IGFBP-2 concentrations were elevated after prolonged fasting. This suggests that prolonged changes in insulin secretion may result in a signi®cant change of IGFBP-2.…”

“…This indicates that IGFBP-2 can quantitatively in¯uence IGF-1 transport and may have some role in regulating IGF-1 bioavailability in obesity, because serum IGFBP-2 are more abundant than IGFBP-1 in adults. 34 …”

Insulin-Like Growth Factors (IGFs) and IGF-Binding Proteins (IGFBP-1, -2 and -3) in Diabetic Pregnancy: Relationship to Macrosomia.

“…Although Langford and Miell [29] reported that cord IGF-I negatively correlated with IGFBP-2, this was not the case in the present study with diabetic patients. It appears that a change in glucose metabolism has little effect, if any, on IGFBP-2 production [39].…”