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.
We found in a previous study that injections of GH for 3 weeks caused nitrogen conservation despite restriction of intake to 24 Cal (100 kJ)/kg ideal BW (IBW). To determine the effects of longer periods of treatment and further caloric restriction on nitrogen balance, lipolysis, and body composition, 20 obese (30-67% over IBW) subjects (16 women and 4 men; 20-54 yr old) were fed a diet of 18 Cal (75 kJ)/kg IBW with 1.2 g protein/kg IBW daily for 13 weeks. During weeks 2-12, 10 subjects received injections of recombinant methionyl GH (0.1 mg/kg IBW every other day), and the other 10 sex-, age-, and weight-matched subjects were given injections of saline. There were no significant differences between the two groups in total weight loss [GH, 13.9 +/- 3.0 (+/- SD) kg; saline, 15.2 +/- 3.8 kg ) or the percentage of body fat lost (GH, 8.1 +/- 2.4%; saline, 7.5 +/- 1.5%), although GH injection caused a significant acute increment in serum FFA concentrations (GH, 0.53 +/- 0.37 mmol/L; saline, 0.08 +/- 0.22 mmol/L; P less than 0.001) throughout the study. This acute lipolytic response to GH decreased significantly, from 0.86 +/- 0.32 mmol/L on day 1 of GH treatment to 0.35 +/- 0.41 mmol/L by day 35 of GH injection (P less than 0.01). Nitrogen balance was significantly more positive in the group receiving GH during the first 33 days of the GH injection period [GH, +0.07 +/- 1.82 g/day (+5.0 +/- 130.0 mmol/day); saline, -1.91 +/- 1.10 g/day (-136.3 +/- 78.5 mmol/day); P less than 0.001]. During the last 44 days of GH injection, however, the nitrogen balance in the two groups was similar [GH, -0.90 +/- 1.65 g/day (-64.2 +/- 117.8 mmol/day); saline, -1.08 +/- 0.95 g/day (-77.1 +/- 67.8 mmol/day); P = NS]. Mean plasma insulin-like growth factor I (IGF-I) concentrations rose from a basal value of 1.6 +/- 0.8 to 2.9 +/- 1.2 U/mL by 48 h after the first GH injection and ranged subsequently from 3.2 +/- 1.3 to 4.9 +/- 3.3 U/mL during GH injection (P less than 0.001). In contrast, the mean IGF-I concentration did not change in the group that received saline. Dietary restriction during the first week of study caused serum T3 concentrations to decline in both groups.(ABSTRACT TRUNCATED AT 400 WORDS)
Insulin-like growth factor I (IGF-I) is a peptide growth factor that circulates bound to carrier proteins. One form of carrier protein (mol wt, approximately 26K) is not believed to be GH dependent, is relatively unsaturated, and modulates the cellular response to IGF-I. This study was undertaken to determine the variables that control the plasma concentration of this protein, which was measured using a specific RIA. The mean plasma 26K IGF-binding protein (IGF-BP) concentration in 15 normal fasting subjects at 0800 h was 9.4 +/- 4.4 (+/- SD) micrograms/L. The mean value in GH-deficient patients was increased to 19.5 +/- 10.1 micrograms/L (n = 60; P less than 0.05), and it was 7.3 +/- 4.3 micrograms/L in patients with acromegaly (n = 31). The GH dependency of these changes is further supported by the observation that subjects who received GH injections had a 51% reduction in their fasting values. Nutritional intake appeared to be a more important controlling variable than GH. During an overnight fast plasma 26K IGF-BP values increased approximately 4-fold in 6 normal subjects. After 2 days of fasting, the mean value in 7 obese subjects rose progressively from 6.5 +/- 2.3 to 11.7 +/- 5.4 micrograms/L (P less than 0.001), and it increased further to 19.2 +/- 5.9 micrograms/L by day 4 of fasting; after 2 days of refeeding it returned to the prefasting level of 6.8 +/- 1.9 micrograms/L. Likewise, ingestion of a standard test meal resulted in a significant decrease in mean plasma 26K IGF-BP from a fasting value of 8.4 +/- 2.9 to 5.6 +/- 2.8 micrograms/L 4 h postprandially (P less than 0.05). In summary, the plasma concentrations of the 26K IGF-I-BP fluctuate widely in response to dietary manipulation, whereas GH status appears to be a secondary controlling variable.
Because weight-reducing diets result in loss of lean body tissue as well as fat, we sought to determine whether injections of GH might facilitate the preservation of nitrogen and accelerate the loss of body fat during dietary restriction. The dietary intake of 8 obese subjects was restricted to 24 Cal/kg ideal BW and 1 g protein/kg for 11 weeks. During weeks 3-5, 4 subjects were given a total of 10 im injections of recombinant methionyl human GH, 1 morning injection every 48 h in a dosage of 0.1 mg/kg ideal BW. The other 4 subjects were given injections of vehicle. During weeks 8-10, the subjects who had received GH previously were given vehicle and vice versa. While receiving GH injections the mean daily nitrogen deficit [0.35 +/- 2.14 (+/- SD) g/day] was significantly less than the loss during injection of vehicle (2.21 +/- 1.45 g/day; P less than 0.001). Although three of six subjects lost 190% more fat (as determined by hydrostatic weighing) while receiving GH, the difference in group mean fat loss during GH injection was not significantly greater than that during injection of vehicle (3.06 +/- 1.39 kg lost with GH vs. 2.64 +/- 1.08 kg lost with vehicle; P = NS). In parallel with the changes in nitrogen balance, GH produced a significant increase in the mean plasma somatomedin-C/insulin-like growth factor I concentration. From a mean pretreatment value of 1.06 +/- 0.28 U/mL, a maximal value of 3.20 +/- 1.60 U/mL was achieved after 12 days of GH injection (P less than 0.001). Somatomedin-C/insulin-like growth factor I concentrations did not change during injection of vehicle. During GH injection weight loss was attenuated because of fluid retention. If weight loss was determined 1 week after the end of GH administration, however, the total weight loss (3.42 +/- 1.73 kg) was not significantly different from that during the 3 weeks of vehicle administration and the following week (4.16 +/- 1.30 kg). Fasting blood glucose and serum insulin concentrations did not change during GH administration, and no glycosuria was detected in morning urine samples. Short term GH administration is effective in decreasing the loss of lean body mass in individuals ingesting restricted diets. However, fat loss was not accelerated.
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