insulin-like growth factor 1 (IGF1)

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The Insulin-Like Growth Factor-1 (IGF1) System as a Potential Biomarker for  Nutritional Status and Growth Rate in Pacific Rockfish (SEBASTES SPP.)

The Insulin-Like Growth Factor-1 (IGF1) System as a Potential Biomarker for Nutritional Status and Growth Rate in Pacific Rockfish (SEBASTES SPP.)

External environmental influences are translated into changes in growth in part via the altered secretion of stimulatory or inhibitory hormones within the somatotropic endocrine axis. Blood hormone concentrations have shown to be easily accessible indicators of growth regulation and metabolism (Möstl and Palme, 2002). The growth hormone (GH)/insulin-like growth factor (Igf) system, specifically, has been shown to be a key regulator of changes in somatic growth with variation in nutritional status (Fuentes et al., 2013; Picha et al., 2008a; Reindl and Sheridan, 2012). Changes in nutritional conditions have been shown to alter liver production of the somatomedin hormone Igf1 in fishes. Given that relationship between Igf1 and nutritional status, it has been proposed that circulating concentrations of Igf1 may serve as a reliable indicator of recent growth rate in fishes (Beckman, 2011; Picha et al., 2008a; Reinecke, 2010). In most vertebrates, insulin-like growth factor-1 (Igf1) is the predominant mediator of growth following activation of the GH/Igf axis (e.g. Duan, 1997; Perez-Sanchez and Le Bail, 1999; Reinecke et al., 2005). In brief, GH secreted from the anterior pituitary binds the GH receptor to stimulate hepatic production of Igf1, which regulates somatic tissue growth by binding Igf1 receptors in target tissues while exerting negative feedback on pituitary GH production (Duan et al., 2010; Fuentes et al., 2013; Le Roith et al., 2001; Wood et al., 2005). Conserved amongst vertebrates, Igf1 regulates growth by promoting cell proliferation, cartilage growth, and skeletal elongation (Reinecke et al., 2005;
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Quantitative trait locus mapping of genes that control body length and plasma insulin like growth factor 1 level in mice

Quantitative trait locus mapping of genes that control body length and plasma insulin like growth factor 1 level in mice

female mice produced by crossing C57BL/6 J females and DDD.Cg-A y males. A congenic DDD.Cg-A y strain was established by introgressing the A y allele from the B6.Cg-A y strain by backcrossing for 12 generations. DDD.Cg-A y females were longer than B6.Cg-A y females; therefore, QTLs that interact with the A y allele may be identified for body length. In addition, QTL analysis was also performed for plasma insulin-like growth factor 1 (IGF1) levels because IGF1 is known to play essential roles in growth and development. If QTLs for IGF1 levels coincide with those for body length, we can gain endocrinological insight into the QTLs for body length.
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Adult growth hormone deficiency treatment with a combination of growth hormone and insulin like growth factor 1 resulting in elevated sustainable insulin like growth factor 1 and insulin like growth factor binding protein 3 plasma levels: a case report

Adult growth hormone deficiency treatment with a combination of growth hormone and insulin like growth factor 1 resulting in elevated sustainable insulin like growth factor 1 and insulin like growth factor binding protein 3 plasma levels: a case report

At this juncture one of us (ERB) considered the use of Increlex® (a mecasermin (rDNA origin) injection). This agent is an aqueous solution for injection containing human insulin-like growth factor-1 (rhIGF-1) produced by recombinant DNA technology. IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 dal- tons. The amino acid sequence of the product is identi- cal to that of endogenous human IGF-1. The rhIGF-1 protein is synthesized in bacteria ( Escherichia coli ) that have been modified by the addition of the gene for human IGF-1. This agent was started at 0.2 mg at bed- time which we found to raise her IGF-1 level to 130 ng/ ml within one month and, as observed in Figure 1, increased by 6 August 2009 to 193 ng/ml, then to 249 ng/ml on 5 September 2009, and finally on 1 January 2010 it was at a high of 395 ng/ml. Surprisingly her IGF-BP3 plasma levels continued to decrease to 2.5 ng/ ml. On 23 November 2009 we re-administered Nordi- tropin® in combination with an increased amount of Increlex® between 1.3 and 1.5 mg. Subsequent to this treatment while her IGF-1 level was maintained at a high level (373 to 395 ng/ml) her IGF-BP3 began to
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Changes in pain and insulin like growth factor 1 in fibromyalgia during exercise: the involvement of cerebrospinal inflammatory factors and neuropeptides

Changes in pain and insulin like growth factor 1 in fibromyalgia during exercise: the involvement of cerebrospinal inflammatory factors and neuropeptides

Approximately one third of FM patients are estimated to suffer from growth hormone (GH) deficiency, with impaired growth hormone responses leading to reduced insulin-like growth factor 1 (IGF-1), a critical mediator of growth hormone [5-7]. A previous study found that GH dysfunction was associated with increased pain scores during an exercise test as well as with higher pre- exercise levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) [8]. Regular exercise is expected to increase the resting level of IGF-1 in healthy individuals [9], but no increase was found in patients with FM who exercised for 6 months [10]. Together with insulin, IGF-1 is a central regulator for cell growth, survival, and energy metabolism in the body and the central nervous system (CNS). The major IGF-binding protein in serum and extracellular fluid is insulin-like growth binding protein 3 (IGFBP3). IGFBP3 did not change significantly in FM patients after 6 months of exercise [10].
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LMP1 Promotes Expression of Insulin-Like Growth Factor 1 (IGF1) To Selectively Activate IGF1 Receptor and Drive Cell Proliferation

LMP1 Promotes Expression of Insulin-Like Growth Factor 1 (IGF1) To Selectively Activate IGF1 Receptor and Drive Cell Proliferation

In keeping with previous reports, expression of LMP1 in- creased the phosphorylation of EGFR (15–17). At the same time, LMP1 decreased the activation of AXL and increased the phos- phorylation of insulin-like growth factor 1 receptor (IGF1R). In- terestingly, activation of insulin receptor (IR), which is closely related to IGF1R, was not altered by LMP1 (Fig. 1C). IGF1R is a tetrameric RTK implicated in the development of multiple cancer subtypes, and its signaling capabilities and role in cellular trans- formation have been extensively reviewed elsewhere (37, 38). Ma- ture IGF1R contains two extracellular alpha subunits linked by disulfide bonds and two membrane-spanning beta subunits that contain intracellular kinase domains and docking sites for adaptor proteins. The alpha subunits of IGF1R have a molecular mass of roughly 130 kDa, while the beta subunits have a molecular mass of approximately 97 kDa and frequently generate the predominant bands detected via immunoblotting (38). Most antibodies that detect phospho-IGF1R (pIGF1R) also cross-react with pIR. To recapitulate the detection method in the protein arrays, cell lysates were immunoprecipitated with anti-IGF1R and probed with anti- pTyr to specifically detect pIGF1R. This approach demonstrated that LMP1 increased the activation of IGF1R in 293T, C666, NP69, MCF10a, and Rat1 cells (Fig. 1D). The C666 cell line con- tains the EBV genome and is thought to express LMP2 and EBV RNAs, with trace levels of LMP1 (33, 36). Expression of exogenous LMP1 in C666 cells induced IGF1R activation in the presence of the EBV genome, indicating that LMP1 can regulate pIGF1R levels in the context of EBV infection. Elevated pIGF1R was detected in cell lines stably (MCF10a and Rat1) and transiently (293T, C666, and NP69) expressing LMP1, indicating that the effects of LMP1 on IGF1R are consistent (Fig. 1D).
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Insulin-like growth factor 1 and 2 (IGF1, IGF2) expression in human microglia: differential regulation by inflammatory mediators

Insulin-like growth factor 1 and 2 (IGF1, IGF2) expression in human microglia: differential regulation by inflammatory mediators

activation phenotypes and IGF1 production, and further suggest that neurotrophic growth factor production is suppressed in a proinflammatory (M1) environment but is encouraged in an M2 environment. In addition to macro- phage cell types, proinflammatory cytokines have also been shown to inhibit IGF1 expression in systemic cells. For instance, IL-1 and TNFα suppress (growth hormone- induced) IGF1 mRNA expression in hepatocytes [55,56]. Despite extensive study, the molecular mechanism underlying regulation of IGF1 transcription is not well understood. The 5 0 regulatory region of the IGF-1 gene contains a cAMP response element (CRE) [57,58]. Hu- man microglial IGF1 expression was increased by db cAMP, suggesting that IGF1 expression in these cells is also under the control of CRE. As many neurotransmit- ters (norepinephrine, dopamine, and so on) activate the cAMP/protein kinase A (PKA) pathway, these results suggest that IGF1 expression can be facilitated in the neural environment. Conversely, under chronic neurode- generative conditions (such as Alzheimer’s disease and Parkinson’s disease), growth factors levels can be depleted, as a result of selective neurotransmitter deficiencies. The effect of proinflammatory mediators on IGF1 expression might in part be explained as a consequence of their role in cAMP/CRE activation. Together, these results indi- cate intriguing relationships between neural environment, growth factor production, and neuroinflammation [59,60]. Regulation of IGF2 has been extensively studied in tu- mors, with little information available on non-neoplastic cells. IGF2 is an imprinted gene and has an important role during mouse development [16,20,25,61]. Excess IGF2 is produced during fetal stage and failure of re- moval of excess IGF2 due to IGF2R deficiency results in fatal organ overgrowth due to overstimulation of IGF1R. Less is known about the post-developmental role of IGF2, but in human beings, IGF2 production continues after birth. IGF2, similar to IGF1, signals through IGF1R with resulting cell survival, growth, and metabolic effects mediated by the PI3K/Akt pathways. In our investiga- tion, IGF2 expression was uniquely upregulated by LPS (in contrast to IGF1) in human microglia, (and by IL-1β in astrocytes in culture), suggesting that the two IGF peptides are under different regulatory controls. Several sequences identified in the human IGF2 promoter in- clude Sp1, Egr-1-like, C/EBP, and AP-1 sites [61], some of which are inducible by LPS. Future studies are neces- sary to elucidate the molecular mechanisms underlying differential microglial IGF peptide expression.
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Current trends and challenges in cancer management and therapy using designer nanomaterials

Current trends and challenges in cancer management and therapy using designer nanomaterials

EPR: enhanced permeability and retention; FDA: Food and Drug Administra- tion; PEG: polyethylene glycol; DOX: doxorubicin; IGF1: insulin-like growth factor 1; IONPs: iron oxide nanoparticles; PDX: patient-derived xenograft; MRI: magnetic resonance imaging; AMF: alternating magnetic field; EGFR: epider- mal growth factor receptor; FR: folate receptor; MSNs: mesoporous silica nano- particles; siRNA: small interfering RNA; FITC: fluorescein isothiocyanate; RITC: rhodamine B isothiocyanate; PLGA: poly(lactic-co-glycolic acid); PVA: polyvinyl alcohol; PDDAC: poly(diallyldimethylammonium chloride); PDT: photodynamic therapy; PSMA: prostate-specific membrane antigen; CTAB: cetyltrimethylam- monium bromide; CNTs: carbon nanotubes; MWCNTs: multi-walled carbon nanotubes; NIR: near-IR; BSA: bovine serum albumin; SCID: severe combined immunodeficiency; GO: graphene oxide; CD: β-cyclodextrin; DEN: dendrimer; CPT: camptothecin; PpIX: protoporphyrin IX; OSCC: oral squamous cell carci- noma; MUC1: Mucin 1; Lf: lactoferrin; PLA: polylactic acid; DTX: docetaxel; TMZ: temozolomide; BBB: blood–brain-barrier; PAMAM: polyamide amine; DHA: docosahexaenoic acid; HEP-mPEG: heparin-functionalized monomethoxy PEG. Authors’ contributions
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<p>Downregulated level of insulin in COPD patients during AE; role beyond glucose control?</p>

<p>Downregulated level of insulin in COPD patients during AE; role beyond glucose control?</p>

There is an urgent need to explore the pathophysiological mechanism of AECOPD, which will give future clues for new anti-in fl ammation target therapies. It has been reported that many molecules are upregulated during the AE process. Chen et al conducted a systematic review. Interleukin-6, C-reactive protein (CRP), and tumor necrosis factor-alpha were the most frequently studied biomarkers. 2 In our previous studies, we found that levels of serum insulin-like growth factor binding protein 7 (IGFBP7) level was raised during AECOPD. Similar to the expression pattern of CRP, the IGFBP7 levels reduced after convalescence from AE. 3 IGFBP7 belongs to IGFBP superfamily, which are a group of homologous proteins repre- senting an important link between insulin and insulin-like growth factor (IGF) systems. IGFBP7 binds IGF at least 5- to 25-fold lower, and insulin 500-fold higher than conven- tional IGFBP1-6. 4 Ye et al demonstrated that insulin-like growth factor 1 (IGF1) level was decreased in AECOPD serum. 3,5 Insulin, IGF1 and IGFBP form the important insu- lin/IGF1/IGFBP network. However, the role of insulin in AECOPD was not clear.
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Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis

Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis

Solid biological evidence connects insulin-like growth factor 1 (IGF1) with the regulation of endothelial cell func- tion. Vascular endothelial and smooth muscle cells express IGF1 receptor (IGF1R), which mediates angio-protective effects of IGF1. Locally produced IGF1 supports prolifera- tion and migration of endothelial progenitors essential for blood vessel reparation and controls oxidative stress trig- gered by inflammation [16 – 18]. Circulating IGF1 is known to induce vasodilation, which contributes to the regulation of arterial BP and vascular tone, while deletion of IGF1 in mice enhanced mechanisms of vasoconstriction leading to hypertension. Clinically, both a direct and inverse relation between IGF1 levels and BP has been reported. Early studies with focus on patients with congenital or acquired abnormalities in GH/IGF1 production, indicated an asso- ciation between high IGF1 production and hypertension [19, 20]. Recent studies of general population with low prevalence of obvious endocrinological conditions reported an inverse association between IGF1 and BP [21 – 24]. Low serum IGF1 is tightly linked to vascular changes in aging [25] and obesity [26] and to the increased cardiovascular morbidity and mortality [27 – 30].
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Insulin like growth factor 1 stimulation of lymphopoiesis

Insulin like growth factor 1 stimulation of lymphopoiesis

osmotic minipumps for 7 or 14 d. Mice were weighed daily and bled at sacrifice; the spleen and thymus were harvested and single cell suspensions were made for analysis of cell phenotype and cell number. The responses of splenocytes to mitogens (concanavalin A, lipopolysaccharide, and pokeweed mitogen), alloantigens and dinitrophenyl ovalbumin were measured. After either 7 or 14 d of treatment, rhIGF-1 had an overall whole-body anabolic effect, resulting in increased body and organ weights with prominent increases in the weight of the spleen and thymus. Furthermore, the rhIGF-1 treated mice were
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Association of insulin like growth factor I gene polymorphisms (IGF1/TasI and IGF1/SnaBI) with the growth and subsequent milk yield of Polish Holstein Friesian heifers

Association of insulin like growth factor I gene polymorphisms (IGF1/TasI and IGF1/SnaBI) with the growth and subsequent milk yield of Polish Holstein Friesian heifers

one is (CA) n dinucleotide repeat polymorphism located in the P1 promoter (Kirkpatrick et al., 1992) within which the A/C transversion was identified at position –977 bp upstream from the ATG codon in exon 1 (GenBank Acc. No. DQ975234)( Zych et al., 2007). Also, the C/T transition (GenBank Acc. No. AF017143) (Ge et al., 2001) was found at position –512 bp. A 4-bp deletion (TTTG) within intron 4 and one SNPs within intron 5 (IGF1/ DpnII polymorphism) were detected by Lien et al. (2000) (GenBank Acc. No. AF210383-387). Nine novel SNPs within introns and 3’UTR were geno- typed by Mullen et al. (2011). In addition, Whole Genome Shotgun (WGS) libraries contain about 100 SNPs and their number still increases. Many researchers have shown an association between the IGF1 genotypes and milk yield and composi- tion (Curi et al., 2005; Siadkowska et al., 2006; Bonakdar et al., 2010; Mehmannavaz et al., 2010; Szewczuk et al., 2011) as well as growth traits in various cattle breeds (Li et al., 2004; Siadkowska et al., 2006; Reyna et al., 2010). The studies con- ducted so far have mainly been focused on the milk performance in Holstein-Friesian cattle, whereas there is no information on the association between the IGF1 gene polymorphism and the growth and development of calves and their subsequent yield as adult individuals.
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GENETIC AND NON-GENETIC THEORIES ON THE ETIOLOGY OF POLYCYSTIC OVARY SYNDROME: A REVIEW

GENETIC AND NON-GENETIC THEORIES ON THE ETIOLOGY OF POLYCYSTIC OVARY SYNDROME: A REVIEW

Recent studies showed that insulin-like growth factors (lGFS) play an important and complex role in ovarian physiology. Hammond and colleagues29 were the first to demonstrate the ovarian secretion of IGFS. Insulin-like growth factor 1 (lGF-l) can actively induce insulin resistance and increase adrenal androgen secretion.ls It i s likely that IGF - l stimulates E2 production by a combination of granulosa cell proliferation and stimulation of the aromatase complex.3o It may also act as an amplifier of FSH action by interacting with the FSH transduction signal at multiple cellular sites.31 In vitro experiments with PCO granulosa cells show that physiological concentrations of IGF-l and FSH act synergistically to control E2 production.32
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Expression and clinical significance of IGF-1, IGFBP-3, and IGFBP-7 in serum and lung cancer tissues from patients with non-small cell lung cancer

Expression and clinical significance of IGF-1, IGFBP-3, and IGFBP-7 in serum and lung cancer tissues from patients with non-small cell lung cancer

Abstract: The expression and clinical significance of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), and insulin-like growth factor bind- ing protein 7 (IGFBP-7) were investigated in serum and lung cancer tissues from 57 patients with non-small cell lung cancer (NSCLC). Lung cancer tissues at different pathologic stages (27 patients at stages I–II and 30 patients at stages III–IV), normal lung tissues from 17 patients with benign pulmonary disease, and serum samples from both lung cancer and benign pulmonary disease patients were collected during surgery. Enzyme-linked immunosorbent assay and avidin- biotin-peroxidase complex immunohistochemical staining were used to detect IGF-1, IGFBP-3, and IGFBP-7 expression in serum and tissues, respectively. The results show that expression of IGF-1 in lung cancer tissues and serum from NSCLC patients were significantly higher than in the control (P , 0.05). However, expression of IGFBP-3 and IGFBP-7 in cancer tissues and serum from NSCLC patients was significantly lower than in the control (P , 0.05). These results suggest that upregulation of IGF-1 and downregulation of IGFBP-3 and IGFBP-7 may be potential diagnostic biomarkers for NSCLC.
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Original Article Bufalin inhibits invasion and metastasis in colorectal cancer cells through miRNA-497 mediated IGF1R-PI3K-Akt signaling pathway

Original Article Bufalin inhibits invasion and metastasis in colorectal cancer cells through miRNA-497 mediated IGF1R-PI3K-Akt signaling pathway

Abstract: Objective: Bufalin, a major active ingredient of the Chinese traditional medicine Venenum Bufonis, exerts anti-tumor activity in multiple cancers. This study aimed to assess the role and mechanism of bufalin in invasion and metastasis inhibition in colorectal cancer. Methods: Human colorectal carcinoma Lovo cells were treated with bufa- lin at different concentrations, and cellular function and proliferation, as well as the expression of related molecules were evaluated. Results: Bufalin inhibited the proliferation of colorectal cancer cells in a time- and dose-dependent manner. Further mechanistic assessment showed that miR-497 down-regulation promoted invasion and metastasis in colorectal cancer cells by effecting the insulin-like growth factor 1 receptor (IGF1R)-Phosphoinositide 3 kinase (PI3K)-Protein Kinase B (Akt) signaling pathway. Meanwhile, bufalin could reverse these changes. Conclusion: the current findings suggested that bufalin could inhibit invasion and migration in colorectal cancer cells through miR- NA-497 mediated IGF1R-PI3K-Akt signaling.
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Combined sprint and resistance training abrogates age differences in somatotropic hormones

Combined sprint and resistance training abrogates age differences in somatotropic hormones

The aim of this investigation was to compare serum growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) in re- sponse to a combined sprint and resistance training (CSRT) program in young and middle- aged men.Thirty-eight healthy, moderately trained men participated in this study. Young and middle-aged men were randomly assigned to, a young training group (YT = 10, 21.4± 1.2yrs) ora young control group (YC = 9, 21.6±1.8 yrs), a middle-aged training group (MAT = 10, 40.4±2.1 yrs) or a middle-aged control group (MAC = 9, 40.5±1.8 yrs). Participants per- formed the Wingate Anaerobic Test (WAnT) before and after a 13-week CSRT program (three sessions per week). Blood samples were collected at rest, after warm-up, immedi- ately post-WAnT, and 10 min post-WAnT. CSRT induced increases in GH at rest and in response to the WAnT in YT and MAT (P<0.05). CSRT-induced increases were observed for IGF-1 and IGFBP-3 at rest in MAT only (P<0.05). Pre-training, GH, IGF-1 and IGFBP-3 were significantly higher at rest and in response to the WAnT in young participants as com- pared to their middle-aged counterparts (P<0.05). Post-training, YT and MAT had com- parable basal GH (P>0.05). In response to the WAnT, amelioration of the age-effect was observed between YT and MAT for IGF-1 and IGF-1/IGFBP-3 ratio following CSRT (P> 0.05). These data suggest that CSRT increases the activity of the GH/IGF-1 axis at rest and in response to the WAnT in young and middle-aged men. In addition, CSRT reduces the normal age-related decline of somatotropic hormones in middle-age men.
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Genetic variation in insulin like growth factor signaling genes and breast cancer risk among BRCA1 and BRCA2 carriers

Genetic variation in insulin like growth factor signaling genes and breast cancer risk among BRCA1 and BRCA2 carriers

The IGFBPs serve as growth modulators, both independently and as regulators of IGFs [37-39]. IGFBP5 and IGFBP2 are overexpressed in breast cancer tissues [40,41], and are involved in apoptosis [42-44]. In a study of African Americans, with replication in Nigerians, we reported significant associa- tions of SNPs within the IGFBP2 to IGFPB5 region and the risk of breast cancer [45]. These two genes are in a tail-to-tail configuration separated by only 10 kb on chromosome 2q, so it is possible the same underlying causal variation results in an association with both genes. In the present study, we report a significant association of IGFBP2 SNP rs9341134, also observed in the previous study [45], and marginally significant associations with variants in IGFBP5. Resequencing is needed to try to identify the actual causal variant. Another piece of evidence that this region may be associated with breast cancer is the association of SNP rs13387042 with a 1.2-fold increased risk in breast cancer, reported in a deCODE genome-wide association study [46] - with replica- tion by the Cancer Genetic Markers of Susceptibility project (odds ratio = 1.2) [47], by the Breast Cancer Association Consortium (odds ratio = 1.14) [48], and by the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (HR = 1.14 and HR = 1.18 for BRCA1 and BRCA2 carriers, respec- tively) [49]. It is hypothesized that this SNP may act as a long- range regulatory element on expression of IGFBP2 or IGFBP5 [46].
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Building Muscle: The Role of Insulin-Like Growth Factor Binding Protein-6 and Insulin-Like Growth Factors in the Differentiation of Placental Mesenchymal Stem Cells into Skeletal Muscle

Building Muscle: The Role of Insulin-Like Growth Factor Binding Protein-6 and Insulin-Like Growth Factors in the Differentiation of Placental Mesenchymal Stem Cells into Skeletal Muscle

The IGF family plays a central role in muscle development, differentiation, growth, and regeneration (14-16, 30, 31). IGFBPs are the carriers for IGFs in the circulation (7), protecting them from degradation (6, 32), and delivering them to specific tissues and thus modulating the biological actions of IGFs. Also, IGFBPs increase the half-life of the IGF peptides in the circulation and control their access to the IGF-1R, thus playing an important role in IGF regulated cell metabolism, development, and growth. In recent years, it has become apparent that the IGFBPs have functions independent of IGFs (8). Several IGF-binding proteins have been shown to be important in myogenesis and are expressed in developing muscle cells. Ren et al. reported that in C2C12 myoblast cells and in primary skeletal muscle cells, IGFBP-5 acts in an IGF-dependent manner to promote myogenesis by binding to IGF-2 and promoting its interaction with the IGF-1R (33). Knockdown of IGFBP-5 impaired myogenic differentiation by reducing myogenin, myosin heavy chain, and IGF-2 expression (33). In L6E9 skeletal myoblasts, IGFBP-4 and IGFBP-6 were accumulated during myogenesis, with IGFBP-4, not IGFBP-6, inhibiting IGF-1 induced muscle differentiation (34). These findings suggested the important role of IGFBPs in the differentiation of both primary cell lines of skeletal muscle lineage. Our study is the first to demonstrate the role of IGFBP-6, which is specific for the embryonic IGF, IGF-2, in muscle development using PMSCs.
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Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study

Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study

Background: In Sri Lanka, there exists chronic kidney disease of both known (CKD) and unknown etiologies (CKDu). Identification of novel biomarkers that are customized to the specific causative factors would lead to early diagnosis and clearer prognosis of the diseases. This study aimed to find genetic biomarkers in blood to distinguish and identify CKDu from CKD as well as healthy populations from CKDu endemic and non-endemic areas of Sri Lanka. Methods: The expression patterns of a selected panel of 12 potential genetic biomarkers were analyzed in blood using RT-qPCR. Fold changes of gene expressions in early and late stages of CKD and CKDu patients, and an apparently healthy population of a CKDu endemic area, Girandurukotte (GH) were calculated relative to apparently healthy volunteers from a CKDu non-endemic area, Kandy (KH) of Sri Lanka, using the comparative CT method. Results: Significant differences were observed between KH and early stage CKDu for both the insulin-like growth factor binding protein 1 (IGFBP1; p = 0.012) and kidney injury molecule-1 (KIM1; p = 0.003) genes, and KH and late stage CKD and CKDu for the glutathione-S-transferase mu 1 (GSTM1; p < 0.05) gene. IGFBP1 and KIM1 genes showed significant difference between the early and late stage CKDu ( p < 0.01). The glutamate cysteine ligase catalytic subunit (GCLC) gene had significantly different expression between KH and all the other study groups ( p < 0.01). The GH group was significantly different from the KH group for the oxidative stress related genes, G6PD, GCLC and GSTM1 ( p < 0.01), and also the KIM1 gene ( p = 0.003). IGFBP1, insulin-like growth factor binding protein 3 (IGFBP3), fibronectin 1 (FN1) and KIM1 showed significant correlations with serum creatinine, and IGFBP1, KIM1 and kallikrein 1 (KLK1) with eGFR ( p < 0.05).
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Targeting insulin-like growth factor axis in hepatocellular carcinoma

Targeting insulin-like growth factor axis in hepatocellular carcinoma

The majority of IGF-1 is synthesized in the liver under the influence of growth hormone, which is a major pro- moter of postnatal growth [18]. However, deletion of liver specific IGF-1 gene in mice showed no difference in growth compared to wild type animals, even though serum IGF-1 level was reduced by 75% [18-20]. Such observations came with no surprise when later on IGF-1 was found to be produced in other organs such as the kidneys, muscle and bone [16]. IGF-1 can act as an autocrine, paracrine or endocrine growth factor, there- fore even minimal amount of IGF-1 could still exert its function on postnatal growth [18-20]. Nutrition deple- tion reduced IGF-1 levels and risk of cancer [12,21], whereas infusion of IGF-1 abolished the protection against carcinogenesis provided by dietary restriction [22]. Epidemiology studies also indicate that IGF-1 is involved in the risk of cancer development. Several stu- dies suggest that height and weight at birth are propor- tional to the level of IGF-1 in the umbilical cord, and that infants with higher percentile of height and weight at birth tend to develop more common cancers such as breast, prostate and colorectal later in life [22-28]. (B) IGF-2
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Insulin-like Growth Factor Binding Proteins.pdf

Insulin-like Growth Factor Binding Proteins.pdf

muscle cells secrete a serine protease for insulin like growth insulin-like growth factor binding proteins 1 and 3 on. factor binding protein-2[r]

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