Serum Concentrations Of IGF-II Research Articles

The Prospective Association Between Plasma Concentrations of Cellular Growth Factors and Risk of Heart Failure Mortality in Japanese Population.

BackgroundLimited evidence is available on the association of insulin-like growth factors (IGFs) and risk of heart failure in population-based samples. We investigated whether serum IGFs concentrations can predict mortality from heart failure.MethodsWe conducted a nested case-control study of 39,242 subjects aged 40–79 years who participated in the JACC study, a large Japanese prospective cohort study; participants provided serum samples and were followed up for 9 years. In heart failure cases and age-, sex-, community-, and year of blood withdrawal-matched controls, we measured serum concentrations of IGF-I, IGF-II, and IGF binding protein 3 (IGFBP3) and transforming growth factor (TGF-β1).ResultsDuring the follow-up, there were 88 heart failure deaths (44 men and 44 women). Each increment of 1 standard deviation [SD] of IGF-II (120.0 ng/mL in women and 143.7 ng/mL in men) was associated with a 47% reduced risk of mortality from heart failure; multivariable odds ratio was 0.53 (95% confidence interval [CI], 0.30–0.94, P-trend = 0.03). The multivariable odds ratio in the highest quartile of IGFBP3 serum concentrations (≥3.29 µg/mL in women and ≥3.31 µg/mL in men) compared with the lowest (<2.11 µg/mL in women and <2.56 µg/mL in men) was 0.24 (95% CI, 0.05–1.11; P-trend = 0.12). No association was found between serum concentrations of IGF-I or TGF-β1 and risk of heart failure.ConclusionsHigher serum concentrations of IGF-II were associated with lower mortality from heart failure, which might suggest a possible role of IGF-II in the occurrence or prognosis of heart failure.

Mo1609 Obesity Drives Colon Tumor Development in AOM-Treated Mice

Background/Aims: Obesity is an important risk factor for colon cancer in humans. Numerous studies in experimental animals demonstrated that a high fat diet enhances colon cancer development. A potential mechanism for this increased risk is that adipose tissue, a major source of adipokines, growth factors, and cytokines promotes tumor growth. Alternatively, a high-fat diet causes metabolic changes that can independently enhance tumor growth. Here we determined the independent effects of these factors on colon tumor development. Methods: C57BL/6J male mice were fed regular chow or high fat diet (HFD) for 8 weeks. Half of the animals on high fat diet were switched to regular chow, and half on regular chow were switched to the HFD with the resulting 4 groups being regular (R), HFD (H), regular switched to HFD (RH) and HFD switched to regular (HR). One week after the switch, 5 weekly doses of azoxymethane (AOM) were given to induce colon tumors. Mice were euthanized 1 day after the final dose of AOM to analyze gene expression, proliferation, and apoptosis in the colon or 25 weeks after AOM to analyze numbers of colon tumors and aberrant crypt foci (ACF). Body composition was measured by echo MRI. Results: We previously showed the significantly increased tumor multiplicities in all groups that received HFD (groups H, HR, and RH) relative to animals on regular diet (group R). In this study, an ELISA based array analysis of cytokines and growth factors in serum revealed that obesity was associated with differential expression of molecules involved in insulin-like growth factor (Igf) signaling. Relative to group R mice, group HR mice had ratios 1.5, 0.7, and 0.75 in serum concentrations of Igf-II, Igf binding protein (Igfbp) 5, and Igfbp6, respectively (p = 0.05 for each). These differences were also reflected in mRNA expression patterns in mesenteric adipose tissue, as all obese groups had significantly elevated expression of Igf-I and Igf-II and significantly depressed expression of Igfbp5 and 6. Group HR mice appeared to have a greater toxic response to AOM relative to all other groups as measured by apoptotic index and lengthening of the Ki67-positive proliferative zone in colonic crypts following AOM treatment. Conclusions: We have identified obesity itself as a tumor promoter. A mechanism for the increased tumor responses may involve heightened signaling through the Igf1-receptor due to increased expression of ligands and decreased expression of binding proteins in mesenteric adipocytes. Additionally, the greater tumor response of mice in HFD that were switched to regular diet likely involves a heightened toxic response to AOM. Supported by NIH RO-1 DK60729 (CP); A Pilot and Feasibility Study from CURE: Digestive Diseases Research Center 41301; and the Martin Blinder Fund for IBD Research

The changes of sera IGF-II and VEGF concentrations before and after microwave ablation treat-ment in rat models of bepatoceilular carcinoma

Objective To study change of IGF- Ⅱ , VEGF, IL-2 and IFN-γ before and after microwave ablation in rat models of hepatocellular carcinoma （HCC）. Methods Eighty SD rats were randomly divided into 4 groups as follows ： normal group, control group, microwave ablation group and surgical operation group. The HCC models were established in control group, microwave ablation group and surgical operation group. The microwave ablation group and surgical operation group accepted microwave ablation and surgical operation respectively. The serum concentrations of IGF-Ⅱ , VEGF, IL-2 and IFN-γ were determined by ELISA. IGF-Ⅱ, VEGF, IL-2, AFP and IFN-γ concentrations between the normal and control groups were compared after treatment for 3 weeks. Results In control group, sera concentrations of IGF- Ⅱ（ 1.93± 0.45 vs 1.16 ± 0. 21 ）μg/L, and VEGF （395.72 ± 55.28 vs 248.43 ±41.71 ） ng/L on the 5th week were significantly higher than those on the 3rd week （ P 〈 0.05 ）. After microwave ablation or surgical operation, concentrations of IGF- Ⅱ （0.65 ±0.18 vs 0. 73 ±0.16） μg/L and VEGF （ 129.35 ±51.46 vs 135.63 ± 33.37） ng/L were significantly decreased,but IL-2, and IFN-γ concentrations significantly increased as compared with control group. Conclusion IGF- Ⅱ can promote tumor angiogenesis directly or by increasing the synthesis of VEGF. It could be an important index in diagnosis, prognosis and tracking of primary HCC. Microwave ablation is an effective method in the treatment of HCC. Key words: Carcinoma, hepatocellular; Insulin like growth factor; Vascular endothelial cell growth factor; Cytokine ; Microwave ablation

No Effect of Red Clover–Derived Isoflavone Intervention on the Insulin-Like Growth Factor System in Women at Increased Risk of Colorectal Cancer

Increased insulin-like growth factor (IGF)-I and IGF-II concentrations are related to increased colorectal cancer risk. Isoflavones have been associated with reduced colorectal cancer risk, and may affect the IGF system because of their weak estrogenic activity. The aim of the study was to investigate the effect of isolated isoflavones on serum concentrations of IGF system components. We conducted a randomized, placebo-controlled, double-blinded, crossover trial in four hospitals in the Netherlands to investigate the effect of an 8-week supplementation with red clover-derived isoflavones (84 mg/d) on serum IGF-I concentrations. In addition, serum concentrations of IGF-II and IGF binding proteins (IGFBP)-1, IGFBP-2, and IGFBP-3 were assessed. Normal colorectal tissue biopsies were obtained after the first intervention period and mRNA expression of IGF-I, IGF-II, IGFBP-3, and IGF-IR was evaluated. Our study population consisted of 34 postmenopausal women with a family history of colorectal cancer or a personal history of colorectal adenomas. Isoflavone supplementation did not significantly affect serum concentrations of total IGF-I (mean relative within-person difference; IGF-I, -2.0%; 95% confidence interval, -8.0% to 3.9%). IGF-II and IGFBPs were also not significantly altered after isoflavone supplementation. Colorectal tissue mRNA expression of IGF system components did not significantly differ between individuals on isoflavone supplementation and those who received placebo. The results of our trial, supported by a qualitative review of soy trials published to date, suggest that isoflavones do not significantly affect circulating levels of IGF system components. Increased levels of IGF-I, as observed in most of these trials, are likely due to simultaneous protein supplementation.

Effects of estradiol implantation on growth, carcass traits and circulating concentrations of insulin-like growth factors (IGFs) and IGF-binding protein-3 in finishing barrows

Eighty crossbred barrows aged 120 to 141 days and weighing 71.2±0.8 kg were randomly divided into eight pens, after which each of 40 animals in four pens was implanted with 24 mg of estradiol-17β (E 2; Compudose®). The animals were allowed an unrestricted access to water and a finisher diet containing 16% crude protein and 3.4 Mcal DE/kg and slaughtered at 107.4±0.8 kg. Blood samples were obtained by jugular venipuncture at day 0 before the implantation and at days 21 and 42. Serum concentration of E 2 increased between days 0 and 21 after the implantation and declined to a level above that of day 0 ( P<0.01) by day 42. E 2 implantation caused a decrease ( P<0.01) in feed intake and backfat thickness and a tendency ( P=0.08) of decreased average daily gain. However, feed conversion efficiency (FCE; live weight gain/feed intake) did not change due to the implantation ( P=0.20). The E 2 implantation did not affect physicochemical characteristics of longissimus muscle including percentages of protein ( P=0.17) and fat ( P=0.43), 24-h pH ( P=0.39), drip loss ( P=0.99), L* (lightness; P=0.78) and a* (redness; P=0.49) values. Serum concentration of insulin-like growth factor (IGF)-I decreased between days 0 and 21 ( P<0.01) and also between days 21 and 42 ( P<0.05) in unimplanted pigs, but not in implanted pigs ( P>0.05), which resulted in a greater ( P<0.05) mean IGF-I concentration in the implanted vs. unimplanted group. By contrast, serum concentrations of IGF-II and IGF-binding protein-3 did not differ between the two groups ( P>0.05). In summary, results suggest that E 2 suppresses voluntary feed intake and backfat deposition without significantly affecting growth efficiency and muscle characteristics in barrows and that effects of E 2 may be partly mediated by IGF-I.

Endocrine and metabolite responses to porcine growth hormone administered by sustained release implant for different lengths of time in male pigs.

The effects of long term administration of GH on serum concentrations of hormones and metabolites was investigated in intact and castrate male swine. At 10 weeks of age, male swine were assigned to six treatments (n = 10/group): nonimplanted intact and castrate males; intact males implanted for 6 weeks, from 22-28 weeks of age; intact males implanted for 12 weeks, from 16-28 weeks of age; and intact and castrate males implanted for 18 weeks, from 10-28 weeks of age. Recombinant porcine GH was administered with sustained release implants designed to deliver a dose of 4 mg/day for 6 weeks. Throughout the study, blood samples were collected, and serum was harvested to quantitate circulating concentrations of glucose, urea nitrogen, GH, insulin, insulin-like growth factor I (IGF-I), IGF-II, and PRL. The pattern of administered GH in the serum suggests that the presence of testes and prior treatment with GH influence GH clearance. Somatotropin treatment elevated serum concentrations of GH and increased serum levels of glucose, insulin, IGF-I, and IGF-II in both intact and castrate animals. However, during the prepubertal period of 10-16 weeks, GH-treated intact males were resistant to the diabetogenic actions of GH, whereas significantly increased serum levels of glucose and insulin occurred in GH-treated castrates during this period. Changes in serum levels of IGF-I throughout the study and in insulin after the first 6 weeks followed the pattern of circulating GH concentrations in the treated animals. Serum concentrations of IGF-II were increased after GH administration, but, in contrast to the IGF-I response, IGF-II levels remained elevated as GH concentrations waned in the latter portion of the implant period. The maintenance of higher serum levels of IGF-II may be less dependent upon GH than are insulin and IGF-I. Administration of GH to intact males is more efficacious in altering metabolites and hormones, with the exception of IGF-I, during the peripubertal and postpubertal periods than during the prepubertal period.

Endocrine and metabolite responses to porcine growth hormone administered by sustained release implant for different lengths of time in male pigs

The effects of long term administration of GH on serum concentrations of hormones and metabolites was investigated in intact and castrate male swine. At 10 weeks of age, male swine were assigned to six treatments (n = 10/group): nonimplanted intact and castrate males; intact males implanted for 6 weeks, from 22-28 weeks of age; intact males implanted for 12 weeks, from 16-28 weeks of age; and intact and castrate males implanted for 18 weeks, from 10-28 weeks of age. Recombinant porcine GH was administered with sustained release implants designed to deliver a dose of 4 mg/day for 6 weeks. Throughout the study, blood samples were collected, and serum was harvested to quantitate circulating concentrations of glucose, urea nitrogen, GH, insulin, insulin-like growth factor I (IGF-I), IGF-II, and PRL. The pattern of administered GH in the serum suggests that the presence of testes and prior treatment with GH influence GH clearance. Somatotropin treatment elevated serum concentrations of GH and increased serum levels of glucose, insulin, IGF-I, and IGF-II in both intact and castrate animals. However, during the prepubertal period of 10-16 weeks, GH-treated intact males were resistant to the diabetogenic actions of GH, whereas significantly increased serum levels of glucose and insulin occurred in GH-treated castrates during this period. Changes in serum levels of IGF-I throughout the study and in insulin after the first 6 weeks followed the pattern of circulating GH concentrations in the treated animals. Serum concentrations of IGF-II were increased after GH administration, but, in contrast to the IGF-I response, IGF-II levels remained elevated as GH concentrations waned in the latter portion of the implant period. The maintenance of higher serum levels of IGF-II may be less dependent upon GH than are insulin and IGF-I. Administration of GH to intact males is more efficacious in altering metabolites and hormones, with the exception of IGF-I, during the peripubertal and postpubertal periods than during the prepubertal period.

Stimulation of statural growth by recombinant insulin-like growth factor I in a child with growth hormone insensitivity syndrome (Laron type)

We studied the effects of 9 months of treatment with twice-daily subcutaneous injections of insulin-like growth factor I (IGF-I), 120 micrograms/kg per dose, in a 9.7-year-old child with growth hormone insensitivity syndrome, in whom short-term studies had suggested that IGF-I might promote linear growth. Height velocity increased from 6.5 cm/yr (+1.7 SD score) to 11.4 cm/yr (+8.8 SD score). Serum concentrations of IGF-I increased from pretreatment values of 9 +/- 2 micrograms/L to a peak of 347 +/- 26 micrograms/L after 2 hours. Serum concentrations of IGF-II were unchanged. Basal but not stimulated growth hormone concentrations were decreased. During the first 12 days of treatment, serum concentrations and the 24-hour urinary excretion of urea nitrogen were decreased by 28% and 10%, respectively (p < 0.05), there was a 2.4-fold increase in urinary excretion of calcium (p < 0.001), and creatinine clearance and urine volume increased by 22% and 55%, respectively (p < 0.02). The changes in serum levels of urea nitrogen and in urinary calcium and creatinine clearance were still evident at 10 weeks. Fasting and postprandial serum glucose concentrations remained normal. We conclude that IGF-I given as twice-daily subcutaneous injections is effective in stimulating statural growth without producing the hypoglycemia and hyperglycemia observed when IGF-I is infused continuously.

Differential tissue regulation of the insulin-like growth factors in rats bearing the MStT/W15 pituitary tumor.

The content of insulin-like growth factors, IGF-I and IGF-II, was measured in tissues of rats bearing a transplantable mammosomatotrophic tumor, MStT/W15. Serum IGF-I was elevated in tumor-implanted rats [2,557 +/- (SE) 419 vs. 891 +/- 100 ng/ml], and tumor tissue concentrations of IGF-I were increased (321 +/- 16 ng/g) in comparison to control liver tissue (160 +/- 5 ng/g) or control pituitary (80 +/- 3 ng/g). The IGF-I levels were significantly increased in most peripheral tissues in the tumor-bearing rats with the exception of the liver. In support of this finding, messenger RNA for prepro IGF-I was likewise not increased in the livers of tumor-bearing rats, nor was there an increase in the growth hormone-dependent IGF-binding protein, BP-3, in the liver or serum of these animals. All tumors had detectable levels of prepro IGF-I mRNA which was, however, less than 50% of that noted in normal control liver. The tumors also expressed an IGF-BP which was identified as IGF-BP-2 by immunoblotting. Serum concentrations of IGF-II were similar in control and tumor-bearing animals (approximately 70 ng/ml). IGF-II levels in the tumor (90 +/- 5 ng/g) were significantly higher than levels in control liver (34 +/- 2 ng/g), but similar to those found in normal pituitary (165 +/- 24 ng/g). In peripheral tissues, IGF-II concentrations were selectively increased in skeletal muscle and heart of tumor-bearing rats. These data demonstrate tissue-specific regulation of IGF-I and IGF-II. Paradoxically, the liver does not appear to be stimulated over control levels by high serum growth hormone levels, since neither IGF-I peptide, IGF-I mRNA, nor IGF-BP-3 levels are increased in livers of tumor-bearing rats. This suggests that the increase in serum IGF-I in these animals is due to increased production of IGF-I by the tumors themselves and by nonhepatic peripheral tissues and further that hepatic responsiveness to growth hormone is diminished in these tumor-bearing animals.