Variants Of Insulin-like Growth Factor Research Articles

Genetic Variants of Insulin-Like Growth Factor 1 (IGF-1) Gene and Their Relationship with Productive Traits in Ross 308 Broilers

This study aimed to investigate the relationship between different genetic variants of the insulin-like growth factor 1 IGF-1 gene and some productive traits in Ross 308 broilers. A total of 150 one-day-old chicks were reared under good management conditions based on the rearing guide and a free-range feeding system. The birds were numbered, and their weights were recorded weekly to calculate weekly weight gain. Other weekly body measurements were also taken. After the rearing period, blood samples were collected from the birds via the wing vein, followed by slaughter and weighing of the carcass to determine the dressing percentage. The main and secondary cuts were weighed, and chest dimensions were measured. DNA was extracted, and three genetic structures were identified using sequencing technology, including GG, GT, and TT, with genetic structure proportions of 0.34, 0.58, and 0.08, respectively. The allele frequencies of G and T were 0.63 and 0.37, respectively. The results showed a significant superiority (P≤0.05) in weight and weekly weight gain for the TT genetic variant in the third, fourth, and fifth weeks compared to the other genetic variants (GT and GG). The TT variant also exhibited superiority in chest circumference in the third and fifth weeks and chest width in the third week. On the other hand, the TT and GG genetic variants showed superiority in chest width in the second and fourth weeks. The TT variant also demonstrated superiority in carcass weight and chest length compared to the other genetic variants. Moreover, the study revealed a significant increase (P≤0.05) in the dressing percentage, relative weight of the chest, wings, and back for the GT and GG genetic variants compared to the TT genetic variant. The GT variant also showed superiority in the relative weight of the thighs. However, there were no significant differences among the genetic variants in the relative weight of the neck and chest depth.

Molecular characterization, expression pattern and genetic variant of insulin-like growth factor 2 mRNA-binding protein 3 gene in goose (Anser cygnoides)

ABSTRACT As a member of the insulin-like growth factor mRNA binding proteins (IGFBPs) family, IGF2BP3 plays important role in skeletal muscle development by regulating IGF2, which has been considered a key gene related to growth and reproductive traits in many agricultural animal species. However, study on the goose IGF2BP3 gene is still scarce. In this study, the full-length cDNA sequence of goose IGF2BP3 gene was cloned and characterized. The goose IGF2BP3 cDNA is 1825 bp in length, containing an open reading frame (ORF) of 1755 bp that encodes a protein of 584 amino acids, which consists of two RNA-recognition motifs (RRMs) and four K-homologous (KH) domains. RT-qPCR analysis indicates that the IGF2BP3 mRNA expression level is the highest in ovary tissue, followed in hypothalamus, spleen, leg muscle and liver, and low level in breast muscle and muscular stomach of the adult Zhedong White goose. Meanwhile, 25 single nucleotide polymorphisms (SNPs) and 5 insertions/deletions (InDels) variants were identified in about 10,764 bp of goose IGF2BP3 genomic DNA sequence. These results serve as a foundation for further investigations of the function of IGF2BP3 gene in geese.

Marie-José Walenkamp: paediatric endocrinologist whose research focused on genetics in growth

At the start of her fellowship in paediatric endocrinology at Leiden University Medical Center (LUMC), a shy, and still largely unknown, Marie-Jose Walenkamp chanced on a patient who appeared to...

Novel alternative splice variant of IGF-1R and its mRNA expression patterns in BaMa and Landrace pigs

The transcript variants of Insulin-like growth factor 1 receptor (IGF-1R) and their expression profiles had never been illuminated in pigs until now. Herein, we identified IGF-1R AS02 as a novel splice variant of IGF-1R gene by RT-PCR and analyzed its mRNA expression level by qRT-PCR in liver, cartilage and muscle tissues, while also detecting the single-nucleotide polymorphism (SNP) site near the splice site of the IGF-1R gene (in intron 19) of BaMa and Landrace pigs. Results demonstrated that the IGF-1R AS02 variant showed a significantly (P less than 0.05) higher expression level in cartilage than in muscle and liver across two pig breeds respectively. The expression level of the normal transcript (IGF-1R ISO01) of IGF-1R in cartilage was markedly lower than that in the other two tissues (P less than 0.05). In cartilage, IGF-1R ISO01 expression was higher in BaMa than in Landrace (P less than 0.05), while the expression level of IGF-1R AS02 was lower in BaMa than in Landrace (P less than 0.05). The SNP was detected in intron 19 of the IGF-1R gene of BaMa and Landrace pigs. These results contributed to facilitating a better understanding of IGF-1R gene in pigs.

Splicing factor-modulated generation of mechano growth factor regulates physiological processes in osteoblasts under mechanical stimuli

ABSTRACTMechanical stimuli influence various physiological processes in osteoblasts. We previously showed that mechano-growth factor (MGF), a splicing variant of insulin-like growth factor 1, is highly expressed in osteoblasts in response to mechanical stimuli. This study aims to explore the systemic functions of MGF in osteoblasts, and the mechanisms by which mechanical stress regulates the alternative splicing of Igf1 to generate MGF. We found that MGF promoted the proliferation and migration of osteoblasts, while it inhibited their differentiation via Erk1/2 pathway. Furthermore, cyclic stretching upregulated the expression of ASF/SF2, which in turn regulated the expression of MGF. Our findings indicate that mechanical stimuli influence the physiological responses of osteoblasts by increasing the expression of MGF, which is regulated by splicing factors.

Association of allele variants of IGF-I, GH and PIT-1 genes with production traits of Birkivska Barvista chicken breed

The article considers the questions about association between allelic variants of insulin-like growth factor I (IGF-I), growth hormone (GH) and pituitary transcription factor-1 (PIT-1) genes with the egg productivity of the Borkovskaya Barvistaya chicken breed. Using classical PCR and PCR-RFLP methods, the PstI-polymorphism in the 5'UTR fragment of the IGF-I gene, HinfI-polymorphism in the promoter fragment of IGF-I gene, AluI-polymorphism in the fourth intron of the GH gene and indel polymorphism in the second intron of the PIT-1 gene were determined. As a result of the studies the significant differences in egg weight values on 30 weeks of life for HinfI-polymorphism in the promoter fragment of the IGF-I gene were revealed. For individuals with the C/C genotype was specific the large values of this index compared to A/A (51,7 ± 0,61 vs. 47.9 ± 0,92 respectively). For PstI-polymorphism in the 5'UTR of the IGF-I gene was shown the prevalence in the number of eggs for 12 weeks of productivity for individuals with the C1C1 genotype compared to C2C2 (65,2 ± 3,77 vs. 60,9 ± 1,33), but in this case the differences are not significantly, what can be caused by a small number of individuals with C1C1 genotype (12). There were no significant differences for other loci.

Maternal citrulline supplementation enhances placental function and fetal growth in a rat model of IUGR: involvement of insulin-like growth factor 2 and angiogenic factors

Objective: To determine the effects of maternal citrulline supplementation on fetal growth and placental efficiency in a rat model of intrauterine growth restriction (IUGR) induced by maternal protein restriction.Methods: Pregnant Sprague–Dawley rats were randomly assigned to three groups: NP (receiving a control 20% protein diet), LP (a 4% protein diet), or LP-CIT (an LP diet along with L-citrulline, 2 g/kg/d in drinking water). On the 15th and 21st day of gestation (GD15 and GD21, respectively), dams underwent a C-section, by which fetuses and placentas were extracted. The expression of genes involved in placental growth and angiogenesis was studied by quantitative RT-PCR.Results: Maternal citrulline supplementation increased fetal weight at GD21, and fetal weight/placental weight ratio, an index of placental efficiency, from mid gestation (p < 0.001). The expression of Igf2-P0, a placenta-specific variant of insulin-like growth factor 2 (Igf2) gene, and Vegf and Flt-1, involved in angiogenic pathways, was enhanced in the LP-CIT group (versus NP, p < 0.001, p < 0.01, and p < 0.05 for Igf2-P0, Vegf, and Flt-1, respectively).Conclusions: In a model of IUGR induced by protein deprivation, citrulline enhances fetal growth, placental efficiency, and the expression of genes involved in angiogenesis. The relevance of such effect in human pregnancies complicated by IUGR warrants further study.

Polymorphisms of Insulin-Like Growth Factor 1 Pathway Genes and Breast Cancer Risk.

Genetic variants of insulin-like growth factor 1 (IGF1) pathway genes have been shown to be associated with breast density and IGF1 levels and, therefore, may also influence breast cancer risk via pro-survival signaling cascades. The aim of this study was to investigate associations between IGF1 pathway single nucleotide polymorphisms (SNPs) and breast cancer risk among European and East Asian women, and potential interactions with menopausal status and breast tumor subtype. Stratified analyses of 1,037 cases and 1,050 controls from a population-based case–control study were conducted to assess associations with breast cancer for 22 SNPs across 5 IGF1 pathway genes in European and East Asian women. Odds ratios were calculated using logistic regression in additive genetic models. Polytomous logistic regression was used to assess heterogeneity by breast tumor subtype. Two SNPs of the IGF1 gene (rs1019731 and rs12821878) were associated with breast cancer risk among European women. Four highly linked IGF1 SNPs (rs2288378, rs17727841, rs7136446, and rs7956547) were modified by menopausal status among East Asian women only and associated with postmenopausal breast cancers. The association between rs2288378 and breast cancer risk was also modified by breast tumor subtype among East Asian women. Several IGF1 polymorphisms were found to be associated with breast cancer risk and some of these associations were modified by menopausal status or breast tumor subtype. Such interactions should be considered when assessing the role of these variants in breast cancer etiology.

Abstract 192: Mechano-growth Factor (MGF) and Cerebral Vasospasm (CV) Post Aneurysmal Subarachnoid Hemorrhage (aSAH)

Cerebral vasospasm (CV) and related ischemic injury is a major contributor to death and disability after aneurysmal subarachnoid hemorrhage (aSAH). Our overall goal is to understand molecular mechanisms of action of endogenous mechano-growth factor (MGF), a splice variant of insulin-like growth factor 1 (IGF-1), in the brain. MGF was found to be neuroprotective after stroke in a gerbil model of ischemic injury and may serve as a potential therapeutic target to prevent CV-induced brain damage. In our studies, we characterized hypoxia induced changes in MGF expression in different brain regions, commonly affected by CV, at different time points (from 2 hours to 7 days) post 4h hypoxia treatments (6, 8,10 or 12% oxygen). The brain regions analyzed were motor cortex, hippocampus, striatum and hypothalamus. In addition, we characterized changes in MGF expression in microparticle (MP) fractions isolated from cerebrospinal fluid (CSF) extracted from CV patients. Microparticle fractions were isolated from CSF samples using serial ultracentrifugation. We used real time RT-PCR, western blots, and enzyme immunosorbent assay to quantify changes in gene expression and protein levels. In the animal model, our results showed that there were time, dose and brain region specific changes in MGF expression that correlated with changes in the expression of heme oxygenase 1 (HO-1) and biliverdin reductase A, which are molecules involved in neuroprotection, and caspases, apoptotic markers. These results suggest that changes in endogenous MGF due to hypoxia may activate neuroprotective pathways in the brain. In CSF MPs isolated from CV patients, we observed an increase in MGF expression that correlated with the CV onset window and with an increase in HO-1, suggesting that similar pathways are activated post-CV in humans and post-hypoxia in animals. These data indicate that endogenous MGF may play a role in CV onset and may be a neuroprotective target in CV papteins. However, further studies are required to elucidate the molecular mechanisms of MGF and its exact role in CV development and patient outcome.

Exploring the genetic variants of insulin-like growth factor II gene and their associations with two production traits in Langshan chicken

ABSTRACTInsulin-like growth factor II (IGF-II) is one of the members of the somatotropic axis which controls the growth and development of animals. This study was conducted to identify single-nucleotide polymorphisms in the IGF2 gene and study their associations with two production traits in a Chinese indigenous chicken (Langshan chicken) population. Genetic variants within the IGF2 gene were screened through PCR-SSCP and DNA sequencing methods. A C6707G mutation (Chromosome 5 position 13,161,038 build 4) was identified. Associations between the mutations of the gene with two production traits were analysed. The results showed that individuals within the GG genotype had significantly higher 16-week-old body weight than those within the CG genotype. In addition, the GG individuals also had significantly higher 300 days egg numbers than individuals within CC or CG genotype. Ratios of dominance effects to absolute values of additive effects were less than 0 for both traits implying that Langshan chickens with homozygous genotypes for this locus had higher performance than individuals with heterozygous genotypes.

Mechano growth factor E peptide promotes rat bone marrow-derived mesenchymal stem cell migration through CXCR4-ERK1/2

Mechano growth factor (MGF) is a splicing variant of insulin-like growth factor 1 (IGF-1). The unique C-terminal E domain of MGF (MGF-E) makes it distinct from the other variants of IGF-1. Our previous work demonstrated that MGF-25E induces the migration of rat bone marrow-derived mesenchymal stem cells (rMSCs) by altering their mechanical properties, which is accompanied by the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. However, the relationship between ERK1/2 activation and the change in mechanical properties has not been illustrated. In the present study, we determined that MGF-25E induced the migration of rMSCs by modulating CXCR4 to activate the ERK1/2 pathway. The analysis of the Young’s modulus and F-actin remodeling indicated that MGF-25E increased the stiffness and the F-actin polymerization of rMSCs through the activation of the CXCR4-ERK1/2 pathway. For the first time, this study clarified the signaling pathway that regulates the mechanical properties of rMSCs and is responsible for MGF-25E-promoted migration.

Functional and transcriptomic analysis of the regulation of osteoblasts by mechano‐growth factor E peptide

Mechano-growth factor (MGF), a splice variant of insulin-like growth factor I (IGF-I), was discovered by Goldspink and colleagues in 1996; since then many studies have implicated MGF as an important local tissue repair factor. Although the short 24-amino-acid C-terminal peptide of MGF (MGF-Ct24E) has a variety of biological activities, its role in bone formation has not yet been clarified. Accordingly, the aim of this study was to investigate the role of MGF-Ct24E in the proliferation, differentiation, and mineralization of rat calvarial osteoblasts. Interestingly, although MGF-Ct24E significantly increased the proliferation and retarded the differentiation of osteoblasts during the first 3 days, prolonged treatment with MGF-Ct24E for up to 3 weeks promoted cell differentiation. To determine the molecular mechanisms behind this plurality, we carried out global transcriptional profiling of osteoblasts in response to MGF-Ct24E and identified differentially expressed genes by bioinformatics analysis. Gene ontology analysis indicated that MGF-Ct24E enhanced the expression of genes associated with osteoblast proliferation and the cell cycle and downregulated genes involved with osteoblast differentiation, skeletal system, and bone development. Moreover, KEGG pathway-based analysis indicated that MGF-Ct24E directly altered focal adhesion and cell cycle progression, in addition to regulating the actin cytoskeleton and gap junctions. In conclusion, MGF-Ct24E has a marked ability to increase bone formation by increasing cell proliferation and delaying cell differentiation during prophase, as well as by stimulating osteoblast differentiation during the advanced stage. The mechanism of action of MGF-Ct24E during the initial stages of bone formation in vitro involves upregulation of the expression of genes involved in proliferation and cell cycle progression, and the repression of differentiation-related genes.

Insulin-Like Growth Factor I (IGF-1) Ec/Mechano Growth Factor – A Splice Variant of IGF-1 within the Growth Plate

Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

Synthesis, characterization, and biocompatibility of a novel biomimetic material based on MGF‐Ct24E modified poly(D, L‐lactic acid)

Mechano-growth factor (MGF) is an alternative splicing variant of Insulin-like growth factor I. MGF and its 24 amino acid peptide analog corresponding to the unique C-terminal E-domain (MGF-Ct24E) are the positive regulator for tissue regenesis in bone. A novel biomimetic poly(D, L-lactic acid) (PDLLA) modification was designed and synthesized based on MGF-Ct24E grafted maleic anhydride modified PDLLA (MPLA). MGF-Ct24Es were grafted into the side chain of MPLA via a stable covalent amide bond using 1-ethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide as the condensing agent to produce biomimetic MPLA materials (MGF-Ct24E-MPLA). Fourier transform infrared spectrometry, amino acid analyzer, and elementary analysis were used to characterize the MGF-Ct24E-MPLA. The hydrophilicity of MGF-Ct24E-MPLA was evaluated by means of the water-uptake ratios and static water contact angle. Data revealed that the grafting efficiency of MGF-Ct24E was about 29.9%. MGF-Ct24E-MPLA had better hydrophilicity than PDLLA and MPLA. The osteoblasts behavior of proliferation, differentiation, and mineralization on PDLLA, MPLA, and MGF-Ct24E-MPLA films was investigated and the results indicated that the introduction of MGF-Ct24E could improve osteoblasts proliferation, mineralization, and delay differentiation. The MGF-Ct24E modified MPLA with higher bioactivity may have potential application for bone tissue engineering.

Characterization and identification of a C‐terminal amidated mechano growth factor (MGF) analogue in black market products

Mechano growth factor (MGF) is a splice variant of insulin-like growth factor that possesses anabolic properties and has not yet been approved for therapeutic use. Nevertheless, it is readily available on the black market. Although the World Anti-Doping Agency (WADA) has banned the use of MGF in sports, no routinely performed methods have been reported for its detection. In this work, two preparations from the black market containing an unknown MGF analogue were characterized. Mass spectrometry characterizations of unknown preparations and a reference human MGF were performed on an Orbitrap and a triple quadrupole mass spectrometers after separation by liquid chromatography. High accuracy measurements allowed protein identification from full scan MS data, and low-resolution full scan MS/MS provided further information on fragmentation. HCD scans of the analytes showed the presence of common b series product ions in the black market preparations and the human MGF reference standard, but all the y series ions starting from (y(1))(+) exhibited a difference of 1 m/z unit in nominal mass. This difference was demonstrated to be due to a C-terminal amidation of MGF. High-resolution data demonstrated that the black market products were both C-terminal amidated analogues of human MGF. In addition, low-resolution MS/MS characterization revealed a potentially diagnostic transition (m/z 717.8 → 431.1) for the discrimination of C-amidated MGF from the endogenous form. Qualitative identification of a MGF C-terminal amidated analogue in two black market products was successfully achieved. This report demonstrates that illegal MGF preparations are commercially available for use as doping agent in sports.

Expression of Splice Variants of Insulin-Like Growth Factor I and the State of the Myosatellite Cell Pool in the Soleus Muscle in Rats during Gravitational Unweighting and Passive Stretching

Gravitational unweighting is known to induce atrophy and to suppress proliferative processes in the postural muscles; muscle stretching during unweighting allows this atrophy to be overcome. It has been suggested that stretching of the soleus muscle promotes proliferation of satellite cells with subsequent incorporation of their nuclei into fibers on functioning loading of the hindlimbs in rats. The numbers of satellite cells labeled with M-cadherin on cross-sections of single fibers were assessed. After two weeks of antiorthostatic suspension, the number of labeled cells decreased by 33% from the level seen in the control group. In passive stretching, the number of labeled cells was 2.5 times greater than that in suspended animals and 1.7 times greater than in that control animals. The key role in the activation of satellite cells is known to be played by growth factors, including insulin-like growth factor I (IGF-I). Levels of IGF-I expression were measured in the soleus muscle after suspension with stretching, which showed no changes as compared with the suspension without stretching or control groups. Thus, these experiments demonstrated that passive stretching stimulates increases in the proliferation of satellite cells in the soleus muscle of the stretched limb in rats as compared with the level seen in normal conditions, with no changes in the expression of IGF-I or its splice variant MGF.

Alternatively spliced transcripts of Sparus aurata insulin-like growth factor 1 are differentially expressed in adult tissues and during early development

Spliced variants of insulin-like growth factor 1 (IGF-1), a small peptide with a critical role in metabolism and growth, have been identified in various vertebrate species. However, despite recent functional data in mammalian systems suggesting specific roles (e.g. in muscle formation) for their pro-peptides and/or E domains, their function remains unclear. In this study, three alternatively spliced variants of Sparus aurata proIGF-1 (1a, 1b, and 1c) were identified and their expression analyzed. In adult fish, IGF-1 gene expression was observed in various soft tissues (highest levels in liver) and calcified tissues, with IGF-1c being always the most expressed isoform. In developing larvae, each isoform presented a specific pattern of expression, characterized by different onset and extent and consistent with a possible role of IGF-1a and 1b during early post-hatching events (e.g. bone or muscle formation), while IGF-1c would be rather involved in early larvae formation but probably acts in concerted action with other isoforms at later stages. We also propose that, in adults, IGF-1a and 1b isoforms may have a local action, while isoform 1c would assume a systemic action, as its mammalian counterpart. This hypothesis was further supported by in silico analysis of isoform distribution, revealing that only IGF-1c/Ea isoform has been conserved throughout evolution and that other fish isoforms (i.e. 1a and 1b) may be associated with mechanisms of osmoregulation. We finally propose that IGF-1 variants may exhibit different modes of action (systemic or local) and may be involved in different developmental and adaptive mechanisms.

The IGF-I splice variant MGF increases progenitor cells in ALS, dystrophic, and normal muscle

The effects of muscle splice variants of insulin-like growth factor I (IGF-I) on proliferation and differentiation were studied in human primary muscle cell cultures from healthy subjects as well as from muscular dystrophy and ALS patients. Although the initial numbers of mononucleated progenitor cells expressing desmin were lower in diseased muscle, the E domain peptide of IGF-IEc (MGF) significantly increased the numbers of progenitor cells in healthy and diseased muscle. IGF-I significantly enhances myogenic differentiation whereas MGF E peptide blocks this pathway, resulting in an increased progenitor (stem) cell pool and thus potentially facilitating repair and maintenance of this postmitotic tissue.

Poster 90: Expression of Muscular Growth Factor on Passive Stretching in the Rat Skeletal Muscle

Objective: To investigate the effect of muscle growth by passive stretching exercise on the rat skeletal muscle. Design: Case-control study. Setting: University laboratory. Animals: 10 male Wistar rats weighing 250 to 350g. Intervention: Continuous passive stretching of unilateral gastrocnemius muscle under anesthesia by ankle dorsiflexion for 15 minutes a day, and 4 procedures were done within the week. Then muscles were removed and ribonucleic acid (RNA) was extracted. Main Outcome Measure: Semiquantitation of the messenger RNA was done for the mechanogrowth factor, that is, an autocrine variant of insulin-like growth factor secreted from muscle, and myogenin, a myogenic transcription factor that enhances the gene expression of the muscle, using the reverse transcription polymerase chain reaction method. Results: Messenger RNA of the mechanogrowth factor was significantly increased in stretched gastrocnemius muscle as compared with the unstretched contralateral one. The expression of myogenin messenger RNA trend to increase, however, the difference was not significant. Conclusions: Brief passive stretching exercise induces the mechanogrowth factor. This finding suggests that passive stretching may prevent the disuse atrophy of patients in an unconscious state or with neurologic defects.

A strong neuroprotective effect of the autonomous C‐terminal peptide of IGF‐1 Ec (MGF) in brain ischemia

The ischemic stroke is the third leading cause of death in developed countries. The C-terminal peptide of mechano-growth factor (MGF), an alternatively spliced variant of insulin-like growth factor 1 (IGF-1), was found to function independently from the rest of the molecule and showed a neuroprotective effect in vivo and in vitro. In vivo, in a gerbil model of transient brain ischemia, treatment with the synthetic MGF C-terminal peptide provided very significant protection to the vulnerable neurons. In the same model, ischemia evoked increased expression of endogenous MGF in the ischemia-resistant hippocampal neurons, suggesting that the endogenous MGF might have an important neuroprotective function. In an in vitro organotypic hippocampal culture model of neurodegeneration, the synthetic peptide was as potent as the full-length IGF-1 while its effect lasted significantly longer than that of recombinant IGF-1. While two peptides showed an additive effect, the neuroprotective action of the C-terminal MGF was independent from the IGF-1 receptor, indicating a new mode of action for this molecule. Although MGF is known for its regenerative capability in skeletal muscle, our findings demonstrate for the first time a neuroprotective role against ischemia for this specific IGF-1 isoform. Therefore, the C-terminal MGF peptide has a potential to be developed into a therapeutic modality for the prevention of neuronal damage.