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R C Baxter

Publications and source records attributed to R C Baxter.

At least 127 records · Page 7Linked to original sources
PubMed1994

Regulation in vivo of the acid-labile subunit of the rat serum insulin-like growth factor-binding protein complex.

The acid-labile subunit (ALS) and insulin-like growth factor (IGF)-binding protein-3 are glycoproteins that form a complex carrying about 90% of the circulating IGFs. This study investigates the regulation of ALS expression by Northern hybridization, and serum ALS levels by RIA, in the rat. Northern analysis of ALS messenger RNA (mRNA) from adult rat brain, heart, lung, muscle, spleen, testis or ovary, kidney, and liver showed a liver-specific predominant 2-kilobase transcript. The steady state abundance of rat ALS mRNA was greatly reduced in neonatal and weanling liver compared to adult liver, with an age dependence similar to that of rat serum ALS levels. Fasting for 24 or 48 h decreased serum IGF-I and ALS levels, but not hepatic ALS mRNA. Streptozotocin-diabetic rats, untreated or treated with human GH for 5 days, had significantly decreased serum ALS levels and liver ALS mRNA abundance. Insulin treatment normalized serum ALS without fully restoring ALS mRNA. Dexamethasone, an inhibitor of ALS synthesis by hepatocytes, significantly reduced both serum ALS and hepatic ALS mRNA. The discrepancies between hepatic expression and serum ALS levels in fasting and diabetes point to a complex regulatory mechanism in which events at the translational level or later may be as important as regulation of gene expression or mRNA stability.

Acids↗
PubMed1994

Growth hormone (GH) regulation of circulating insulin-like growth factor-I levels during sexual maturation of the GH-deficient dwarf (dw/dw) male rat.

In many mammalian species, circulating levels of insulin-like growth factor-I (IGF-I) rise during puberty. Previous studies manipulating testosterone levels in rats with normal GH secretion suggested that the pubertal IGF-I rise is regulated by an interaction between GH and sex steroids. Therefore, in a reciprocal study, IGF-I levels were examined during sexual maturation of the GH-deficient dwarf (dw/dw) rat which has a selective genetic deficiency of GH but normal sex steroid levels. Male dw/dw rats were treated with daily injections of recombinant human GH (200 micrograms/100 g body weight) or saline vehicle, from 28 to 70 days of age. Sexual maturation was determined to occur primarily between 42 and 63 days of age based on testis and seminal vesicle growth and plasma testosterone levels. GH treatment had no effect on seminal vesicle weights, plasma testosterone or gonadotrophins. GH administration resulted in a 7% increase in absolute testes weight (P < 0.05), but a 50% increase in body weight (P < 0.0001). These results supported previous findings that the reproductive development of dw/dw rats is essentially normal. Untreated dw/dw rats had no rise in IGF-I levels during sexual maturation. In contrast, treatment with GH produced a marked sustained rise in IGF-I levels (P < 0.0001). LIgand blots demonstrated GH induction of IGF-binding protein-3 (IGFBP-3) and an IGFBP cluster at 32 kDa. The initially high immunoreactive IGFBP-1 levels (> 600 ng/ml) decreased by 49 days of age after which untreated dw/dw rats had significantly higher IGFBP-1 levels than GH-treated dw/dw rats (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Regulation of insulin-like growth factor-binding protein-1 in rat serum.

Previous studies support a role for insulin-like growth factor-binding protein-1 (IGFBP-1) in modulating insulin-like growth factor (IGF) availability for glucose homeostasis. We have developed a radioimmunoassay (RIA) for rat IGFBP-1 (rIGFBP-1) and have examined the regulation of circulating levels by nutritional and hormonal status. Rabbit antisera were raised against pure rIGFBP-1, and an assay was established with a sensitivity of 50 pg. In the rat, serum IGFBP-1 concentrations decrease with increasing developmental age. They were highest in fetal rat serum, exceeding 4 mg/L, and decreased to < 0.1 mg/L in adult animals. Serum rIGFBP-1 levels increased during fasting, 6-fold after 24 h and 18-fold after 48 h, and were suppressed to levels identical to ad libitum-fed control rats within 2 h of refeeding. Fasting levels were > 2-fold higher in female than male animals. IGFBP-1 concentrations were suppressed by > 50% in two rat models of insulin resistance. Levels increased in STZ-induced (streptozotocin) diabetes and were suppressed to normal with insulin treatment. Exercise stimulated rIGFBP-1 concentrations in fasting animals. On immunoblotting after SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis), rIGFBP-1 in serum appeared as a doublet with molecular masses at 31 and 33 kD. The components of this doublet did not vary across the range of experimental conditions. These observations indicate that the pattern of regulation of rIGFBP-1 is similar to that seen in previous studies of human IGFBP-1, with age, sex, and nutritional status being important regulators.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Altered ligand specificity of proteolysed insulin-like growth factor binding protein-3.

IGF binding protein-3 (IGFBP-3) undergoes limited proteolysis in human pregnancy serum, altering its electrophoretic mobility and its binding of radioiodinated IGF tracers. IGF-I tracer, monoiodinated on Tyr31, discriminated less than other tracers between intact and proteolysed IGFBP-3. In competitive binding curves using this tracer, intact IGFBP-3 showed comparable reactivity towards IGF-I and analogs with substitutions at Tyr24, Tyr31 or Tyr60. In contrast, proteolysed IGFBP-3 reacted equally with IGF-I and [Ala31]IGF-I (approximately 10-fold lower potency than with intact IGFBP-3), but showed a marked selectivity against [Ser24]IGF-I and [Leu60]IGF-I (approximately 100-fold lower potency than with intact IGFBP-3). The affinity of IGF-I binding to proteolysed, but not intact, IGFBP-3 was increased by the addition of the acid-labile subunit of the IGFBP-3 complex. This study defines more fully the lesion in IGFBP-3 caused by serum proteolysis during pregnancy and demonstrates that tyrosine-substituted IGF-I derivatives are valuable tools in studying IGFBP-3 proteolysis.

Binding, Competitive↗
PubMed1993

Circulating levels of IGFs and IGF binding proteins in human cord serum: relationships to intrauterine growth.

Cord sera were obtained from 44 term, human infants exhibiting various patterns of intrauterine growth and were assayed for IGF-1, IGF-2, and IGFBP-1, 2, and 3 by specific RIAs. Serum levels were correlated with birth weight (BW), ponderal index (PI), and placental weight (PW). Total IGF-1 levels correlated significantly with BW (r = 0.392), PW (r = 0.351), and PI (r = 0.481). By contrast, the correlation of IGF-2 with birth weight was not statistically significant (r = 0.264, P = 0.091). The association of IGF-2 with PI, however, was significant (r = 3.348, P = 0.024). IGFBP-3 exhibited significant correlations with BW, PI, and PW, similar to those seen with IGF-1. IGFBP-1 and IGFBP-2, however, were not significantly related to growth parameters. IGF-1 levels correlated strongly with IGFBP-3 levels (r = 0.646, P = 0.001). By contrast, IGF-1 correlated with the reciprocal of both IGFBP-1 and IGFBP-2. Based upon in vitro affinity constants, theoretical concentrations for each [IGF/IGFBP] complex, free IGFs, and free IGFBPs were calculated for each infant. Multiple regression analysis was performed including all 11 calculated variables and correlated with each growth parameter. This analysis revealed that an integrated expression of IGF activity exhibited stronger correlations with growth than each individual peptide species (BW, r = 0.681; PI, r = 0.660; PW, r = 0.658). These data further support roles for IGF related peptides (IGFRPs) in human fetal and placental growth and suggest regulatory/counterregulatory roles for the IGFBPs. It also supports the hypothesis that individual IGFRPs interact in a complex manner to define 'net IGF activity' in relation to fetal growth and/or metabolic status.

Birth Weight↗
PubMed1993

Characterization of the binding defect in insulin-like growth factor binding protein-3 from pregnancy serum.

During pregnancy, insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) undergoes proteolysis, rendering it undetectable by radioligand binding techniques. This study examines the physical and functional defect in pregnancy IGFBP-3. Ternary complex formation has been measured by the binding of the acid-labile subunit of the circulating IGFBP-3 complex, which also requires IGF-I or IGF-II binding. IGF-depleted pregnancy IGFBP-3, prepared by size-exclusion chromatography at low pH, could not form a ternary complex in the presence of [Tyr60]IGF-I or of an IGF-I analogue extensively altered in the A-domain, whereas analogues altered in the C- or D-domains complexed as well as native IGF-I. After purification by immunoaffinity chromatography, non-pregnancy and pregnancy IGFBP-3 formed ternary complexes with IGF-I equally well, although the pregnancy-proteolysed protein appeared degraded to approximately 30 kDa. On analysis by affinity labelling, cross-linked ternary complexes containing non-pregnancy or pregnancy IGFBP-3 were predominantly 135-140 kDa, with an additional complex of 110-115 kDa in the pregnancy preparation. After reverse-phase h.p.l.c., affinity-isolated pregnancy IGFBP-3 was inactive, whereas the protein from non-pregnancy serum retained activity. Thus pregnancy-proteolysed IGFBP-3 is altered in its specificity for IGF analogues, and is more labile than non-pregnancy IGFBP-3, but shows little impairment in normal IGF binding or ternary complex formation.

Carrier Proteins↗
PubMed1993

Serum "big insulin-like growth factor II" from patients with tumor hypoglycemia lacks normal E-domain O-linked glycosylation, a possible determinant of normal propeptide processing.

The insulin-like growth factor II (IGF-II) gene is overexpressed in many mesenchymal tumors and can lead to non-islet-cell tumor hypoglycemia (NICTH). ProIGF-II consists of the 67 aa of IGF-II with a carboxyl 89-aa extension, the E domain. A derivative of proIGF-II containing only the first 21 aa of the E domain [proIGF-II-(E1-21)] has been isolated by others from normal serum and has O-linked glycosylation. We found that the "big IGF-II" of normal serum, as detected by an RIA directed against residues 1-21 of the E domain of proIGF-II, was reduced in size by treatment with neuraminidase and O-glycosidase. The big IGF-II, which is greatly increased in NICTH sera, was unaffected by neuraminidase and O-glycosidase treatment. We have also shown that big IGF-II from normal serum is retained by jacalin lectin columns and that big IGF-II from NICTH serum was not retained, indicating that it lacked O-glycosylation. Normal O-linked glycosylation may be required for proper peptidase processing of proIGF-II. The lack of normal O-linked glycosylation by tumors may explain the predominance of big IGF-II in NICTH sera. In normal serum, most of the IGF-II is present in a 150-kDa ternary complex with IGF-II binding protein (IGFBP) 3 and alpha subunit. In NICTH serum, however, the complexes carrying big IGF-II are < 50 kDa. We investigated whether big IGF-II of NICTH was responsible for this abnormality. Tumor big IGF-II and IGF-II were equally effective in forming the 150-kDa complex with purified IGFBP-3 and 125I-labeled alpha subunit. Both 125I-labeled IGF-II and 125I-labeled proIGF-II-(E1-21), when incubated with normal serum, formed the 150-kDa complex as detected by Superose 12 exclusion chromatography. We conclude that the nonglycosylated big IGF-II of NICTH serum can form normal complexes with serum IGFBPs. The defective binding in NICTH is attributable to defective IGFBP-3 binding.

Adult↗
PubMed1993

Accumulation of insulin-like growth factor binding protein-3 in conditioned medium of human fibroblasts increases with chronologic age of donor and senescence in vitro.

We have found that insulin-like growth factor binding protein-3 (IGFBP-3) accumulates to higher levels in medium conditioned by a strain of normal fibroblasts at late passage (LP) and a strain derived from subjects with Werner syndrome (WS) of premature aging, compared to medium conditioned by the same normal cells at early passage (EP) (Goldstein et al., Proc. Natl. Acad. Sci. USA, 88:9680-9684, 1991). To explore the generality of this phenomenon with respect to chronological age of donor (in vivo aging) and LP (in vitro senescence) we assayed IGFBP-3 in medium conditioned by 18 normal fibroblast strains at EP and LP and two WS strains at the midpoint of their curtailed replicative lifespans and assessed IGFBP-3 mRNA levels in cells by Northern analysis. The lowest accumulations of IGFBP-3 were found in medium conditioned by fetal cells with progressively increasing amounts postnatally; direct correlations between IGFBP-3 levels and donor age were seen in EP cells 3 days after subculture (during logarithmic growth) r = 0.80, P < 0.001, and 7 days after subculture (at confluence) r = 0.77, P < 0.001. With two exceptions, conditioned medium of cell strains accumulated more IGFBP-3 at LP; IGFBP-3 levels correlated with chronological age after 3 days, r = 0.50, P = 0.05, and after 7 days, r = 0.75, P < 0.001. IGFBP-3 content of WS culture medium fell within the range of LP normal cells. Cumulative IGFBP-3 levels were inversely proportional to the thymidine labeling index, a measure of proliferative vigor. With some exceptions IGFBP-3 mRNA levels were commensurate with the amount of IGFBP-3 accumulated in the medium, suggesting that distal translational and posttranslational mechanisms also regulate IGFBP-3 production in some strains. The trend toward augmented IGFBP-3 output of fibroblasts as a direct function of chronological age and in vitro senescence and as an inverse function of proliferative vigor is consistent with the known inhibitory effect of excess IGFBP-3 on IGF-mediated DNA synthesis and the reduced regenerative potential that is evident during biological aging in vivo.

Aging↗
PubMed1993

Supplementary growth hormone treatment of women with poor ovarian response to exogenous gonadotrophins: changes in serum and follicular fluid insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3).

The effects of supplementary growth hormone (GH) treatment upon insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3) concentrations in serum and ovarian follicular fluid were investigated in women undergoing buserelin human menopausal gonadotrophin (HMG) ovulation induction for in-vitro fertilization. Women (n = 40), aged 24-39 (mean 35 years), who showed poor ovarian responses to HMG, were recruited and randomly divided into two groups. Each patient received two cycles of ovulation induction, one with GH (12 IU/day x 12 days/HMG/buserelin) and another with placebo/HMG. Serum IGF-1 increased substantially during the GH treatment and remained significantly higher than the control 2 days after the last GH injection. Serum IGFBP-3 fell steadily during the placebo/HMG treatment and to a nadir on the day of oocyte retrieval (P < 0.05 compared to serum before any treatment). In contrast, IGFBP-3 was increased (P < 0.01) during the GH administration and returned to the control level 2 days after GH injection. Serum oestradiol concentrations on the eighth day of HMG and the day of human chorionic gonadotrophin (HCG) were not significantly different between the two groups. Serum IGF-1 was highly correlated with IGFBP-3 before any treatment (r = 0.433, P < 0.001). This correlation disappeared after buserelin, placebo/HMG treatment in the control group, but it was maintained during GH/HMG treatment (r = 0.343, P = 0.04). Follicular fluid concentrations of GH and IGF-1, not IGFBP-3 or oestradiol, were significantly elevated in the GH-treated women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Enhancement of the anabolic effects of growth hormone and insulin-like growth factor I by use of both agents simultaneously.

The use of growth hormone (GH) as an anabolic agent is limited by its tendency to cause hyperglycemia and by its inability to reverse nitrogen wasting in some catabolic conditions. In a previous study comparing the anabolic actions of GH and IGF-I (insulin-like growth factor I), we observed that intravenous infusions of IGF-I (12 micrograms/kg ideal body wt [IBW]/h) attenuated nitrogen wasting to a degree comparable to GH given subcutaneously at a standard dose of 0.05 mg/kg IBW per d. IGF-I, however, had a tendency to cause hypoglycemia. In the present study, we treated seven calorically restricted (20 kcal/kg IBW per d) normal volunteers with a combination of GH and IGF-I (using the same doses as in the previous study) and compared its effects on anabolism and carbohydrate metabolism to treatment with IGF-I alone. The GH/IGF-I combination caused significantly greater nitrogen retention (262 +/- 43 mmol/d, mean +/- SD) compared to IGF-I alone (108 +/- 29 mmol/d; P < 0.001). GH/IGF-I treatment resulted in substantial urinary potassium conservation (34 +/- 3 mmol/d, mean +/- SE; P < 0.001), suggesting that most protein accretion occurred in muscle and connective tissue. GH attenuated the hypoglycemia induced by IGF-I as indicated by fewer hypoglycemic episodes and higher capillary blood glucose concentrations on GH/IGF-I (4.3 +/- 1.0 mmol/liter, mean +/- SD) compared to IGF-I alone (3.8 +/- 0.8 mmol/liter; P < 0.001). IGF-I caused a marked decline in C-peptide (1,165 +/- 341 pmol/liter; mean +/- SD) compared to the GH/IGF-I combination (2,280 +/- 612 pmol/liter; P < 0.001), suggesting maintenance of normal carbohydrate metabolism with the latter regimen. GH/IGF-I produced higher serum IGF-I concentrations (1,854 +/- 708 micrograms/liter; mean +/- SD) compared to IGF-I only treatment (1,092 +/- 503 micrograms/liter; P < 0.001). This observation was associated with increased concentrations of IGF binding protein 3 and acid-labile subunit on GH/IGF-I treatment and decreased concentrations on IGF-I alone. These results suggest that the combination of GH and IGF-I treatment is substantially more anabolic than either IGF-I or GH alone. GH/IGF-I treatment also attenuates the hypoglycemia caused by IGF-I alone. GH/IGF-I treatment could have important applications in diseases associated with catabolism.

Adult↗
PubMed1993

Participation in an outreach-based coupon distribution program for free methadone detoxification.

OBJECTIVE: The purpose of the study was to identify characteristics of injection-drug users that predicted whether subjects would redeem a coupon for free methadone detoxification and to determine whether they were more likely to participate in a 90-day detoxification program than in a 21-day program. METHODS: A total of 4,390 current heroin users recruited through street-based outreach programs in Newark and Jersey City, New Jersey, accepted coupons for either 21 or 90 days (randomly determined) of methadone detoxification after they were interviewed about drug use and sexual behavior. Subjects also gave blood samples for HIV testing. Multiple regression analysis was used to determine variables associated with coupon redemption. RESULTS: Of 4,390 coupons distributed, 58.5 percent were redeemed; the 90-day coupons were redeemed at a significantly higher rate (59.9 percent) than the 21-day coupons (56.9 percent). Among coupon redeemers, 43.6 percent had never received formal drug treatment, and 44.9 percent were HIV seropositive. Frequent heroin use, previous drug detoxification, frequent drug injection, cleaning needles with bleach, nonblack race, Hispanic ethnicity, and Newark residence each significantly predicted coupon redemption. CONCLUSIONS: Outreach-based coupon distribution may be used to recruit large numbers of never-treated and HIV-infected drug users into treatment. The 90-day coupon was more effective in facilitating treatment entry.

AIDS Serodiagnosis↗
PubMed1993

Bioavailability of insulin-like growth factors (IGFs) in rats determined by the molecular distribution of human IGF-binding protein-3.

Insulin-like growth factor-binding protein-3 (IGFBP-3) forms a 140-kilodalton (kDa) complex with an acid-labile glycoprotein after complexing with IGF-I or IGF-II. To investigate the bioavailability of circulating IGFs in the rat, we determined the molecular distribution and disappearance of an iv bolus of human IGFBP-3 (130 micrograms/kg). Serum fractions were assayed after size-separation chromatography for human (h) and rat (r) IGFBP-3 with specific RIAs. Within 2 min of injection, 52.9 +/- 1.6% of the hIGFBP-3 appeared in a 140-kDa complex. This form remained in the circulation for hours, whereas hIGFBP-3 in 50- and 30-kDa forms disappeared within 30-60 min. The rapid complexing of hIGFBP-3 to the 140-kDa form did not occur in vitro. Measurement of endogenous rIGFBP-2 indicated that there was minimal exchange of hIGFBP-3 with rIGFBP-3 in the 140-kDa complex within the 60 min of the in vivo study. To determine the importance of IGF-I in regulating the molecular distribution of hIGFBP-3 in serum, the experiment was repeated in streptozotocin-diabetic rats, with total IGF-I levels 50% lower than control values. In these animals, 40.1 +/- 5.2% of the hIGFBP-3 appeared in the 140-kDa complex 2 min after injection, significantly less than that in controls (P < 0.05), and hIGFBP-3 disappeared more quickly from the circulation than in controls (P < 0.05). After coinjection of recombinant human IGF-I, the retention of hIGFBP-3 in the circulation was prolonged in both control and diabetic animals. Because IGFBP-3 must bind IGF before it can associate with the acid-labile subunit, these findings indicate a much greater availability of IGFs to the circulation than previously estimated.

Animals↗
PubMed1993

The composition and distribution of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) in the serum of growth hormone receptor-deficient patients: effects of IGF-I therapy on IGFBP-3.

We have previously reported that adult GH receptor-deficient (GHRD) patients treated subcutaneously with recombinant human insulin-like growth factor (IGF)-I have increased serum IGF-I levels and decreased IGF-II levels, whereas IGF-binding protein-3 (IGFBP-3) levels were unchanged. To further investigate the effects of IGF-I administration upon the IGF-IGFBP axis in GHRD, we have examined: 1) the molecular distribution of IGF-I and IGF-II among the IGFBPs; 2) the composition and distribution of the IGFBPs, in particular IGFBP-3; and 3) the acid labile subunit (ALS). Serum samples from adult GHRD patients who were treated sc with recombinant human IGF-I (40 micrograms/kg, sc, twice a day) or from normal Ecuadorian adults were incubated with [125I]IGF-II and subjected to neutral size-exclusion chromatography. The fractions were then subjected to Western ligand blot, Western immunoblot, IGFBP-3 RIA, and IGF RIAs. Serum of healthy adults incorporated [125I]IGF-II into the 150- and 44-kilodalton (kDa) IGFBP region. The 150-kDa IGFBP region contained most of the circulating IGFBP-3, whereas the 44-kDa IGFBP region contained mainly IGFBP-1, 2, and 4. The 150-kDa region also contained a unique 28-kDa immunoreactive form of IGFBP-3, which was not detectable by Western ligand blot. Endogenous IGF-I and IGF-II were distributed equally in the 150- and 44-kDa IGFBP regions. Sera from GHRD patients mainly incorporated [125I]IGF-II into the 44-kDa IGFBP region. Similar to control sera, the 150-kDa IGFBP region contained IGFBP-3, albeit at lower concentrations. The 44-kDa IGFBP region contained all IGFBPs including 50% of the total immunoreactive IGFBP-3. The two immunoreactive forms of IGFBP 3 (40- to 45-kDa doublet and 28-kDa band) were present in both IGFBP regions. The IGF size-distribution study revealed that the 150-kDa IGFBP region carried half of the circulating endogenous IGF-I, but only 30% of the IGF-II. Concentrations of the ALS were consistently low. Administration of IGF-I to GHRD patients was unable to increase concentrations of the molecular forms of IGFBP-3, correct the aberrant distribution of IGFs among the IGFBPs, or increase serum concentrations of ALS. In conclusion, we have found two forms of IGFBP-3 associated with IGF and ALS, which are capable of forming the ternary 150-kDa complex in healthy adult serum. The ratio of these two forms of IGFBP-3 and their distribution in serum was different between GHRD and control patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Responses of insulin-like growth factor binding protein-1 (IGFBP-1) and the IGFBP-3 complex to administration of insulin-like growth factor-I.

The importance of insulin-like growth factor binding proteins (IGFBPs) in modulating the bioactivity of administered IGFs is poorly understood. This study examines responses of IGFBP-1 and the IGFBP-3 complex to recombinant human IGF-I. Eight fasted subjects received a single dose of 0.1-0.125 mg/kg IGF-I sc. This caused a 10-fold rise in IGFBP-1 over 6 h, falling rapidly after food intake. Peak (6-h) IGFBP-1 values were highly correlated with peak post-prandial (8-h) glucose values (r = 0.941). IGFBP-3 showed little response, decreasing slightly over the 48-h period following IGF-I. Adaptive changes in IGFBPs were studied in fed adults injected daily for 7 days with IGF-I, 0.1 mg/kg sc. Following the first injection, IGFBP-1 had a markedly blunted response compared to that in fasted subjects. However, after the seventh IGF-I injection, a 3.5-fold greater IGFBP-1 response to the same IGF-I dose was seen. Concomitantly with the increased IGFBP-1 responsiveness, mean immunoreactive IGFBP-3 and acid-labile subunit levels decreased significantly (p < 0.005), whereas IGFBP-2 detected by immunoblotting increased. Thus IGF-I administration causes changes in IGFBPs which may be important in regulating IGF-I bioavailability.

Adult↗
PubMed1993

Effect of human insulin-like growth factor-binding protein-1 on the half-life and action of administered insulin-like growth factor-I in rats.

We have determined the effect of human insulin-like growth factor-binding protein-1 (hIGFBP-1) on the circulating half-life (t1/2) of human insulin-like growth factor-I (hIGF-I) and on hIGF-I-stimulated 2-deoxyglucose uptake in tissues of the cannulated conscious rat. The levels of hIGF-I in rat serum were measured by radioimmunoassay. The assay was carried out in the presence of partially purified rat IGF to remove interference from any IGFBPs not removed by acid-ethanol extraction. An intravenous bolus of 12.5 micrograms hIGF-I, given to 12-h fasted rats, disappeared from the circulation in a double exponential fashion with an initial t1/2 of 1.2 +/- 0.2 min (n = 8), which increased to 5.3 +/- 0.9 min when 100 micrograms hIGFBP-1 was co-administered (n = 5; P < 0.001). The second phase of disappearance of hIGF-I indicated an apparent t1/2 of 35.7 +/- 5.6 min which was not significantly altered by the co-infusion of hIGFBP-1. Circulating hIGFBP-1, measured with a primate-specific radioimmunoassay, disappeared in a single exponential fashion with a t1/2 of 8.8 +/- 0.7 min. A tracer amount of 2-deoxy-[1-3H]glucose was administered intravenously at the same time as the peptide(s) and the rate of tissue uptake and phosphorylation of 2-deoxy-[1-3H]glucose determined. Compared with a control group (n = 4), hIGF-I significantly stimulated hexose uptake into heart, soleus and red quadriceps muscles and hIGFBP-1 partially reversed this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗