Increased Plasma Insulin-like Growth Factor-1 Research Articles

Spotlight in Plastic Surgery: January 2023.

Spotlight in Plastic Surgery: January 2023.

Clinical outcome and gut development after insulin-like growth factor-1 supplementation to preterm pigs.

BackgroundElevation of circulating insulin-like growth factor-1 (IGF-1) within normal physiological levels may alleviate several morbidities in preterm infants but safety and efficacy remain unclear. We hypothesized that IGF-1 supplementation during the first 1–2 weeks after preterm birth improves clinical outcomes and gut development, using preterm pigs as a model for infants.MethodsPreterm pigs were given vehicle or recombinant human IGF-1/binding protein-3 (rhIGF-1, 2.25 mg/kg/d) by subcutaneous injections for 8 days (Experiment 1, n = 34), or by systemic infusion for 4 days (Experiment 2, n = 19), before collection of blood and organs for analyses.ResultsIn both experiments, rhIGF-1 treatment increased plasma IGF-1 levels 3-4 fold, reaching the values reported for term suckling piglets. In Experiment 1, rhIGF-1 treatment increased spleen and intestinal weights without affecting clinical outcomes like growth, blood biochemistry (except increased sodium and gamma-glutamyltransferase levels), hematology (e.g., red and white blood cell populations), glucose homeostasis (e.g., basal and glucose-stimulated insulin and glucose levels) or systemic immunity variables (e.g., T cell subsets, neutrophil phagocytosis, LPS stimulation, bacterial translocation to bone marrow). The rhIGF-1 treatment increased gut protein synthesis (+11%, p < 0.05) and reduced the combined incidence of all-cause mortality and severe necrotizing enterocolitis (NEC, p < 0.05), but had limited effects on intestinal morphology, cell proliferation, cell apoptosis, brush-border enzyme activities, permeability and levels of cytokines (IL-1β, IL-6, IL-8). In Experiment 2, rhIGF-1 treated pigs had reduced blood creatine kinase, creatinine, potassium and aspartate aminotransferase levels, with no effects on organ weights (except increased spleen weight), blood chemistry values, clinical variables or NEC.ConclusionPhysiological elevation of systemic IGF-1 levels for 8 days after preterm birth increased intestinal weight and protein synthesis, spleen weight and potential overall viability of pigs, without any apparent negative effects on recorded clinical parameters. The results add further preclinical support for safety and efficacy of supplemental IGF-1 to hospitalized very preterm infants.

Effects of Composite Supplement Containing Collagen Peptide and Ornithine on Skin Conditions and Plasma IGF-1 Levels-A Randomized, Double-Blind, Placebo-Controlled Trial.

Aging-associated changes of skin conditions are a major concern for maintaining quality of life. Therefore, the improvement of skin conditions by dietary supplementation is a topic of public interest. In this study, we hypothesized that a composite supplement containing fish derived-collagen peptide and ornithine (CPO) could improve skin conditions by increasing plasma growth hormone and/or insulin-like growth factor-1 (IGF-1) levels. Twenty-two healthy Japanese participants were enrolled in an 8-week double-blind placebo-controlled pilot study. They were assigned to either a CPO group, who were supplemented with a drink containing CPO, or an identical placebo group. We examined skin conditions including elasticity and transepidermal water loss (TEWL), as well as plasma growth hormone and IGF-1 levels. Skin elasticity and TEWL were significantly improved in the CPO group compared with the placebo group. Furthermore, only the CPO group showed increased plasma IGF-1 levels after 8 weeks of supplementation compared with the baseline. Our results might suggest the novel possibility for the use of CPO to improve skin conditions by increasing plasma IGF-1 levels.

Insulin-like growth factor-1 is associated with life-history variation across Mammalia.

Despite the diversity of mammalian life histories, persistent patterns of covariation have been identified, such as the 'fast-slow' axis of life-history covariation. Smaller species generally exhibit 'faster' life histories, developing and reproducing rapidly, but dying young. Hormonal mechanisms with pleiotropic effects may mediate such broad patterns of life-history variation. Insulin-like growth factor 1 (IGF-1) is one such mechanism because heightened IGF-1 activity is related to traits associated with faster life histories, such as increased growth and reproduction, but decreased lifespan. Using comparative methods, we show that among 41 mammalian species, increased plasma IGF-1 concentrations are associated with fast life histories and altricial reproductive patterns. Interspecific path analyses show that the effects of IGF-1 on these broad patterns of life-history variation are through its direct effects on some individual life-history traits (adult body size, growth rate, basal metabolic rate) and through its indirect effects on the remaining life-history traits. Our results suggest that the role of IGF-1 as a mechanism mediating life-history variation is conserved over the evolutionary time period defining mammalian diversification, that hormone-trait linkages can evolve as a unit, and that suites of life-history traits could be adjusted in response to selection through changes in plasma IGF-1.

Maternal beef and postweaning herring diets increase bone mineral density and strength in mouse offspring

The maternal diet during gestation and lactation affects the long-term health of the offspring. We sought to determine whether maternal and postweaning crossover isocaloric diets based on fish or meat affect the geometry, mineral density, and biomechanical properties of bone in mouse offspring in adulthood. During gestation and lactation, C57BL/6 dams were fed a herring- or beef-based diet. After weaning, half of the pups in each group were fed the same diet as their dams, and half were fed the other diet. Areal bone mineral density (aBMD) and bone mineral content (BMC) of the whole body and lumbar spine were measured in the offspring by dual X-ray absorptiometry at 9 and 21 weeks of age. At 22-26 weeks, tibia bone geometry (length, cortical volumetric (v) BMD, BMC, area and thickness) was analyzed by peripheral quantitative computed tomography, and the biomechanical properties of the tibia were analyzed by the three-point bending test. Plasma insulin-like growth factor-1 was analyzed at 12 weeks. In comparison to the maternal herring diet, the maternal beef diet increased aBMD and BMC in the whole body and lumbar spine of adult offspring, as well as cortical vBMD, BMC, bone area, and thickness at the mid-diaphyseal region of the tibia and the biomechanical properties of tibia strength. In contrast, a postweaning beef diet decreased aBMD in the lumbar spine and BMC in the whole body and lumbar spine compared with a postweaning herring diet, which instead increased plasma insulin-like growth factor-1 levels. The change from a maternal beef diet before weaning to a herring diet after weaning decreased body weight and increased the cortical area, vBMD, BMC, thickness, and strength of the tibia. These significant crossover effects indicate that a preweaning maternal beef diet and a postweaning herring diet are optimal for increasing BMC and bone strength in offspring in adulthood.

Perinatal exposure to low-dose 2,2′,4,4′-tetrabromodiphenyl ether affects growth in rat offspring: What is the role of IGF-1?

BackgroundPolybrominated diphenyl ethers (PBDEs) are a group of environmental contaminants increasing in North America. Few data are available on their growth effects at low doses exposure. ObjectivesOur goal in the present study was to evaluate whether low doses of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), which is the most abundant PBDE found in human samples, affects growth and insulin-like growth factor 1 (IGF-1). MethodsDams were exposed either to the vehicle or low doses of BDE-47 (0.002 and 0.2mg/kgbody weight) every fifth day from gestation day 15 to postnatal day (PND) 20 by intravenous injections. Developmental landmarks, body length and body weight of pups were assessed during the first months of life. A glucose tolerance test was performed on PND 40 and 75. Plasma IGF-1 was analysed in trunk blood on PND 27. ResultsExposure to BDE-47 increased plasma IGF-1 and glucose uptake in male but not in female pups. Developmental landmarks were not influenced by BDE-47 while body weight and body length was increased in both exposed male and female offspring during the first months of development. ConclusionThese results demonstrate alteration of growth in rat offspring induced by BDE-47 at levels found in human population. The possible involvement of the growth hormone–IGF axis is discussed.

Correlation of the plasma level of insulin-like growth factor-1 with the number of aberrant crypt foci in male individuals

In human subjects, aberrant crypt foci (ACF) can be classified as dysplastic or non-dysplastic using magnifying colonoscopy. Dysplastic ACF are thought to be a biomarker for the risk of colorectal cancer (CRC). Hyperinsulinemia and insulin-like growth factor-1 (IGF-1) have also been reported to be associated with an increased risk of CRC. To clarify this association, we investigated the relationship between diabetes risk, IGF-1 and the number of dysplastic ACF. Assessment of the number of dysplastic ACF in the entire colorectum is technically difficult, and we imaged the lower rectum only. Blood collections were taken in the morning on the day of colonoscopy. A total of 512 ACF were counted in 84 male participants, and a correlation was demonstrated to exist between age, body mass index (BMI), fasting blood sugar (FBS), insulin, homeostasis model assessment-insulin resistance (HOMA-IR), plasma leptin levels, plasma IGF-1 levels and the number of dysplastic ACF. A significant association between plasma IGF-1 levels and the number of dysplastic ACF was still demonstrable after adjustment for age, BMI, FBS, insulin, HOMA-IR and plasma leptin levels. Our findings suggest that increased plasma leptin and IGF-1 levels, hyper-insulinemia and insulin resistance may promote the growth of dysplastic ACF. The results of multiple regression analysis revealed that increased plasma IGF-1 levels are associated with the number of dysplastic ACF present, and may be an independent risk factor for CRC. In conclusion, elevated plasma IGF-1 may promote the growth of dysplastic ACF and play a key role in colon carcinogenesis in male individuals.

Effects of dietary protein and growth hormone-releasing peptide (GHRP-2) on plasma IGF-1 and IGFBPs in Holstein steers

This study was conduct to determine the influence of dietary protein on the response of plasma insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding proteins (IGFBPs) to exogenous growth hormone releasing peptide-2 (GHRP-2 or KP 102) in Holstein steers. Eight 16-month-old Holstein steers were grouped by liveweight to two feeding treatments; high protein (HP; CP 1.38 kg/day and TDN 4.5 kg/day DM intake, n = 4) or low protein (LP; CP 0.66 kg/day and TDN 4.42 kg/day DM intake, n = 4). The experiment was a single reverse design whereby each group was injected twice daily with GHRP-2 (12.5 μg/kg body weight (BW)/day) or saline solution into the jugular vein for a 6-day period. Plasma IGF-1 in the HP group were higher than in the LP group ( P < 0.05), but plasma 34 kDa IGFBP-2 was lower in the HP than the LP group ( P < 0.05). The amplitude of the maximum growth hormone (GH) peaks responding to GHRP-2 injection were higher at day 1 than at day 6 of saline or GHRP-2 treatment in both LP and HP steers ( P < 0.05). The area under the GH response curve for 180 min after the GHRP-2 injection was not significantly different between the LP and the HP groups at days 1 and 6. A response in plasma IGF-1 concentration to GHRP-2 treatment in the HP group was observed at day 1 (198.9 ± 18.1 ng/ml), day 2 (195.2 ± 21.1 ng/ml) and day 6 (201.3 ± 14.8 ng/ml) ( P < 0.05). No increase in plasma IGF-1 was observed from GHRP-2 administration in the LP group. Although the response of plasma IGF-1 concentration to GHRP-2 administration was increased in the HP group ( P < 0.05), there was no apparent effect of GHRP-2 treatment on plasma 38–43 kDa IGFBP-3 and 34 kDa IGFBP-2 at days 2 and 6 of treatment. In conclusion, it is proposed that the 34 kDa IGFBP-2 is sensitive to dietary protein level and may play an important role in the regulation of circulating IGF-1 in ruminant. In addition, increased plasma IGF-1 concentration observed in the HP group in response to the GHRP-2 treatment did not appear to affect plasma IGFBPs.

Effect of Twice Daily Administration of GH-releasing Peptide-2 for 10 Days on Growth Performance, Plasma GH Responses and Insulin-like Growth Factor-1 Concentrations in Swine

An increase in frequency of administration of exogenous growth hormone (GH) or GH-releasing hormone was reported to be a model to increase blood circulating insulin-like growth factor-1 (IGF-1) and to improve growth performance in animals. We have investigated the effect of twice daily administration of GH-releasing peptide-2 (GHRP-2) on growth performance, GH responsiveness and plasma insulin-like growth factor IGF-1 in swine. We administered to eight swine, 3 control and 5 treatment, a twice daily s.c. injections of GHRP-2 (30 µg/kg BW) for a period of 10 days. Every day blood samples immediately taken before injections of GHRP-2 or saline, at 08:00 h and 16:00 h, were measured for IGF-1 concentrations. Blood samples for GH assay were collected every 20 min on days 1, 6 and 10, from 1 hour before and 3 h after GHRP-2 or saline injections at 08:00 h. GH peak concentrations and GH area under curve (GH AUC) on day 1, 6 and 10 in treatment group of swine were higher than those in control swine (p<0.05). Twice daily administration of GHRP-2 caused a significantly attenuation (p<0.05) of GH peak concentrations (80.25±13.87, 39.73±5.72 and 27.57±6.06 ng/ml for day 1, 6 and 10, respectively) and GH AUCs (3,536.15±738.35, 1,310.31±203.55 and 934.37±208.99 ng/ml for day 1, 6 and 10, respectively). However, there was no significant difference in GH peak concentration and GH AUC between day 6 and 10. Plasma IGF-1 concentration levels were higher in treatment than control group of swine (p<0.05) after 3 days of the treatment, and the levels reached a plateau from day 3 to 10 of experiment. Growth performance did not alter by GHRP-2 administration, even though a numerical increase of body weight gain and feed efficiency was observed. These results indicate that twice daily administration of GHRP-2 for 10 days in swine did not significantly influence on growth performance, caused an overall attenuation of GH response, and that elevation of plasma GH concentrations caused by GHRP-2 administration increased plasma IGF-1 concentrations, even though an attenuation of GH response was observed. (Asian-Aust. J. Anim. Sci. 2003. Vol 16, No. 8 : 1193-1198)

Growth failure occurs through a decrease in insulin-like growth factor 1 which is independent of undernutrition in a rat model of colitis

BACKGROUNDLinear growth retardation is a frequent complication of inflammatory bowel disease in children. The precise mechanisms causing growth failure are not known.AIMSTo determine the relative contribution of reduced calorie intake...

Further studies on carry-over effects of dietary crude protein and triiodothyronine (T3) in broiler chickens.

Indian River male broiler chickens growing from 7 to 28 d of age were fed on diets containing either 120 or 210 g crude protein and 0 or 1 mg triiodothyronine (T3)/kg diet to study in vitro lipogenesis (IVL). In addition, a carry-over period (180 g crude protein/kg diet from 28 to 40 d of age) was used to test the persistence of prior treatment effects. The higher protein level increased, but T3 decreased (P < 0.01) growth and feed consumption at 28 d of age. The lower protein level increased (P < 0.05) and T3 decreased IVL in 28-d-old chickens. These effects were only sustained for 6 d following the switch to a common diet at 28 d. IVL at 40 d of age was not affected by either crude protein or T3 fed during the 7-28 d period. The higher protein level increased plasma insulin-like growth factor-1 during the period from 7 to 28 d; however, this effect lasted for only 6 d following the switch to a common diet. Plasma growth hormone (GH) at 28 d of age was inversely related to dietary protein level. Changing to a common level of crude protein did not change plasma GH values at 12 d, indicating that the nutritional state of the young chicken may affect GH at a later period of life. Metabolic changes noted in this study were rapid and maintained for a short period of time following the feeding of a common diet.

Effects of growth hormone and insulin-like growth factor 1 (IGF-1 ) on hepatic IGF-1-mRNA, plasma IGF-1 and nitrogen excretion in gastrectomized rats with liver cirrhosis

The growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis is impaired in livercirrhosis. We determined the effects of GH and IGF-1 treatments in gastrectomized rats with thioacetamide-induced cirrhosis. GH did not increase hepatic IGF-1-mRNA, plasma IGF-1 or the tissue, i.e. gastrocnemius muscle IGF-1 level. IGF-1 administration increased plasma IGF-1 without increasing hepatic IGF-1-mRNA. GH and IGF-1 independently decreased postoperative urinary nitrogen excretion. We conclude that both GH and IGF-1 improve postoperative nitrogen metabolism. Furthermore, GH may exert its anabolic effects directly and/or via actions mediated by IGF-1 production, other than in the liver and in the skeletal muscle, in the setting of cirrhosis.

Effect of thyroxine replacement therapy on plasma insulin-like growth factor 1 levels and growth hormone responses to growth hormone releasing factor in hypothyroid patients.

The aim of this study was to evaluate the effect of T4 replacement therapy on plasma insulin-like growth factor 1 (IGF-1) levels in patients with primary hypothyroidism to see whether recovery of pituitary GH responsiveness to GRF was associated with increased plasma IGF-1 levels. IGF-1 levels and GH responses to GRF (1 microgram/kg) were measured in 21 patients with primary hypothyroidism before and after T4 replacement therapy. T4 increased plasma IGF-1 levels (57.2 +/- 4.4 vs 75.9 +/- 8.8 ng/ml, mean +/- SEM, P less than 0.05) and GH responses to GRF as assessed both by peak GH levels (9 +/- 1.5 ng/ml before treatment vs 16.7 +/- 3 ng/ml after treatment, mean +/- SEM, P less than 0.05) and area under curve (496 +/- 92 before treatment vs 896 +/- 161 after treatment, mean- +/- SEM, P less than 0.05). Linear regression analysis showed a positive correlation between free T3 and IGF-1 levels after treatment (r = 0.37, P less than 0.05) and a negative relationship between plasma IGF-1 levels before treatment and delta IGF following T4 replacement therapy (r = 0.45, P less than 0.025). However, no correlation was found between plasma IGF-1 levels and GH responses to GRF, suggesting that GH responses to GRF are of no predictive value in relation to the recovery of plasma IGF-1 levels following T4 replacement therapy in hypothyroid patients.