Muscle Insulin-like Growth Factor Research Articles

Differential Acute Adipogenic Signaling Changes Following Neuromusculoskeletal Injuries

Following traumatic injury, neuromusculoskeletal tissue undergoes extensive plastic modification. Changes can be observed at the local and systemic levels and can involve tissue function, signaling, and local composition. Currently there is limited understanding of early adipogenic changes following some traumatic injuries, which is needed to understand the long-term lack of functional muscle recovery. The objective of this project was to examine plasticity after injury, namely systemic and local adipogenic signaling and fat droplet deposition following volumetric muscle loss (VML) and denervation injuries. We hypothesized there would be differential changes in local and systemic adipogenic signaling, specifically changes in fat droplet accumulation following neuromusculoskeletal injuries. Adult C57B1/6J mice (n=36; 6 male, 6 female/group): posterior compartment VML, tibial nerve denervation, and naïve control. Both injury models target plantarflexor muscles. Mice were euthanized 72-hrs post-injury. In vivo muscle function was assessed, and gastrocnemius, liver, and serum were saved for analysis. Whole gastrocnemius muscles from a subset (n=4/group) were saved for histology, and five standardized sections were systematically obtained 1.5mm apart; muscle sections were stained with H&E and Oil-Red-O to evaluate total fiber number and fat droplet accumulation, respectively. Data were analyzed by two- and three-way ANOVA with Tukey’s HSD post hoc. Maximal torque declined ~81 and 98% following VML and denervation injury, respectively (main effect p<0.001), and VML-injured muscle was more fatigable than injury naïve (main effect p=0.001). Following denervation, liver insulin-like growth factor 1 (IGF-1) was increased ~52% compared to other groups, and was most pronounced in males (main effect injury p<0.001; sex p=0.021). VML injury resulted in a 4-fold higher muscle IGF-1 regardless of sex (interaction p=0.021), and greater muscle interleukin-6 (IL-6), which was more pronounced in females (main effect injury p=0.001; sex p=0.049). Platelet-derived factor growth receptor (PDFGRα) expression was diminished following VML injury in both sexes (interaction p=0.016); suggesting a decrease in fibro-adipogenic progenitors (FAPs) and an alternative origin responsible for increases in IGF-1 and IL-6 rather than FAPs. Serum leptin concentrations were blunted following both VML- and denervation-injury (main effect p=0.002), which may illicit alterations in the regenerative process, specifically the maintenance of muscle quality. Serum IGF-1 and IL-6 concentrations were not affected by injury (p≥0.164). Histological analysis revealed a significant decrease in total fiber number across the middle three sections of the VML-injured muscle (i.e., the section initially injured) compared to other groups (p≤0.034). Findings provide a foundation for characterizing adipocyte development in the muscle remaining after injury and identify therapeutic targets for rehabilitative and nutritional approaches to address contractile and metabolic impairments following injury. Future work should elucidate the time course of adipogenic signaling following these injuries, with particular interest in their relationship to changes in metabolic and contractile impairments. R01-AR078903 (JAC & SMG); University of Minnesota UROP (BAC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The mediating role of lower body muscle strength and IGF-1 level in the relationship between age and cognition. A MIDUS substudy

ObjectiveAging is a natural process associated with a decline in cognition. However, the mediating effect of physical function and circulating myokines on this relationship has yet to be fully clarified. This study investigated how muscle strength and circulating insulin-like growth factor-1 (IGF-1) levels mediate the relationship between age and cognitive functions. Subjects and methodsA total of 1255 participants aged 25–74 years included in the Midlife in the United States II study were retrospectively analyzed. In this cross-sectional analysis, we applied a serial mediation model to explore the mediating effects of muscle strength and circulating IGF-1 levels on the relationship between age and cognitive functions. We included potential confounding factors related to sociodemographics, lifestyle, and health status as covariates in the model. ResultsThe results showed that aging had both direct and indirect effects on cognition. As predicted, muscle strength and IGF-1 levels mediated the relationship between age and specific cognitive functions. In addition, mediation analyses indicated that the association between aging and cognitive flexibility, immediate and delayed memory, and inductive reasoning were partially mediated by muscle strength and IGF-1 levels in a serial manner. ConclusionsOur study demonstrated the serial multiple mediation roles of muscle strength and IGF-1 levels on the relationship between age and specific cognitive functions. Further longitudinal research should be performed to confirm the serial mediation results.

Lower muscle protein synthesis in humans with obesity concurrent with lower expression of muscle IGF1 splice variants.

This study tested the hypothesis that expression of insulin-like growth factor 1 (IGF-1) protein and mRNA splice variants is lower in skeletal muscle of humans with obesity who have a lower mixed-muscle protein fractional synthesis rate (MMP-FSR) when compared with individuals without obesity. The study included nine participants with obesity (OB, mean [SD], BMI = 35 [3] kg/m2 , MMP-FSR = 0.06%/h [0.02%/h]) and nine participants without obesity (W-OB, BMI = 24 [3] kg/m2 , MMP-FSR = 0.08%/h [0.02%/h]; for both BMI and MMP-FSR p < 0.05). MMP-FSR and mitochondrial protein FSR were measured following an overnight fast. Along with lower MMP-FSR, OB participants displayed lower mitochondrial protein FSR (p = 0.03) compared with W-OB participants. Expression of IGF-1 (p = 0.04) and IGF-1 receptor (p < 0.01) proteins was lower in muscle of OB participants. In addition, OB participantshad lower (p < 0.05) mRNA expression of IGF1 variants Eb and Ec. This study demonstrates that lower protein synthesis in muscle of humans with obesity occurs concurrently with lower expression of muscle IGF-1 and IGF-1 receptor proteins, as well as lower mRNA expression of the IGF1 splice variants. These findings indicate that lower protein synthesis observed in muscle of humans with obesity may result from diminished muscle IGF1 gene expression.

Molecular and ultrastructural investigations of the effect of thermal manipulation during embryogenesis on pectoral and thigh muscles growth factors in broilers

Genetic improvement of muscle and meat quantity and quality of broiler chicken over the last 50 yr played a key role in broiler meat production. Thermal manipulation technique has been suggested to promote muscle growth and development. The combination of incubating temperature and timing or duration is very critical to determine the optimum protocol of thermal manipulation which underlines muscle growth improvement. Therefore, this study was to elucidate the optimum timing of thermal manipulation (TM) during embryogenesis on broiler pectoral and thigh muscle growth by assessing muscle growth parameter. This was achieved by analyzing the molecular expression levels of muscle insulin-like growth factor-1 (IGF-1) , growth hormone (GH) and atrogin-1 during embryogenesis and d 35 post-hatch in addition to the measurement of sarcomeres length at d 35 post-hatch. One thousand, four hundred forty fertile eggs were randomly divided and equally into 5 groups. A control (no TM) and 4 thermal manipulated groups TM1, TM2, TM3, and TM4 that thermally subjected to 39°C for 18 h with 65% relative humidity daily during embryonic days ( ED ) ED7-11, ED 11-15, ED 15-18, and ED 7-18, respectively. IGF-1 and GH expression from early thermal manipulated chicks (ED7-11) were significantly higher in both pectoral and thigh muscles when compared to the control ( P < 0.05). This improvement was in parallel with significant improvement in sarcomeres length of the same TM group on post-hatch d 35 ( P < 0.05). On the other hand, Atrogin-1 expression was significantly lower in all treatment groups during post-hatch d 35 compared to the control ( P < 0.05) ( P < 0.05). It can be concluded that TM1 during ED 7-11 leads to improved pectoral and thigh muscles development without adversely affecting their performance. In addition, molecular and ultrastructure investigation of broiler chicken muscles can be used to predict meat quality and may be beneficial for commercial breeders to enhance broiler chicken growth and productivity.

Implications of Insulin-Like Growth Factor-1 in Skeletal Muscle and Various Diseases.

Skeletal muscle is an essential tissue that attaches to bones and facilitates body movements. Insulin-like growth factor-1 (IGF-1) is a hormone found in blood that plays an important role in skeletal myogenesis and is importantly associated with muscle mass entity, strength development, and degeneration and increases the proliferative capacity of muscle satellite cells (MSCs). IGF-1R is an IGF-1 receptor with a transmembrane location that activates PI3K/Akt signaling and possesses tyrosine kinase activity, and its expression is significant in terms of myoblast proliferation and normal muscle mass maintenance. IGF-1 synthesis is elevated in MSCs of injured muscles and stimulates MSCs proliferation and myogenic differentiation. Mechanical loading also affects skeletal muscle production by IGF-1, and low IGF-1 levels are associated with low handgrip strength and poor physical performance. IGF-1 is potentially useful in the management of Duchenne muscular dystrophy, muscle atrophy, and promotes neurite development. This review highlights the role of IGF-1 in skeletal muscle, its importance during myogenesis, and its involvement in different disease conditions.

Dietary clenbuterol modifies the expression of genes involved in the regulation of lipid metabolism and growth in the liver, skeletal muscle, and adipose tissue of Nile tilapia (Oreochromis niloticus)

The current study aimed to evaluate whether clenbuterol, a β2-adrenergic agonist, supplementation in Nile tilapia (Oreochromis niloticus) diets can influence growth and blood parameters. Besides, assessment of adipogenic genes as fatty acid synthase (FAS) and lipoprotein lipase (LPL) which is a key enzyme in the regulation of the flux of fatty acids in liver, muscle, and adipose tissue as well as muscle growth-regulating genes as myostatin (MYO) in muscle and insulin-like growth factor-1 (IGF-1) in liver. The fish were allocated into three equal groups; control group that fed basal diet only and the other two groups fed a basal diet containing clenbuterol at two doses 5 ppm and 10 ppm/kg diet for 30 consecutive days. Results revealed that clenbuterol supplementation significantly increased body weight, decreased liver, spleen and abdominal fat weights, and decreased total circulatory cholesterol and triacylglycerol levels. Moreover, clenbuterol inhibits lipogenesis by downregulation of FAS gene expression by dose and time-dependent manner in the liver while enhanced lipolysis in both the liver and in the adipose tissue. Moreover, lipolysis was reduced in muscle by dose 10 ppm on day 30. Furthermore, clenbuterol presented higher gene expression of MYO and IGF-1 in muscle and liver respectively by dose 5 ppm at day 15 on the other hand, these findings were reversed by day 30 compared with control. In conclusion, clenbuterol efficacy was apparent in a dose and time response pattern to boost growth and reduce fat deposition rates, indicating for the first time that clenbuterol has a profitable growth impact on Nile tilapia.

Regulation of murine skeletal muscle growth by STAT5B is age- and sex-specific

BackgroundSexually dimorphic growth has been attributed to the growth hormone (GH)/insulin-like growth factor 1 (IGF1) axis, particularly GH-induced activation of the intracellular signal transducer and activator of transcription 5B (STAT5B), because deletion of STAT5B reduces body mass and the mass of skeletal muscles in male mice to that in female mice. However, it remains unclear why these effects are sex- and species-specific, because the loss of STAT5B retards growth in girls, but not in male mice. Our objectives were to determine whether sexually dimorphic growth of skeletal muscle persisted in STAT5B−/− mice and investigate the mechanisms by which STAT5B regulates sexually dimorphic growth.MethodsBlood and skeletal muscle were harvested from male and female STAT5B−/− mice and their wild-type littermates from the onset of puberty to adulthood.ResultsGrowth of the skeleton and skeletal muscles was retarded in both sexes of STAT5B−/− mice, but more so in males. Although reduced, sexually dimorphic growth of skeletal muscle persisted in STAT5B−/− mice with an oxidative shift in the composition of myofibres in both sexes. Concentrations of IGF1 in blood and skeletal muscle were reduced in male STAT5B−/− mice at all ages, but only in female STAT5B−/− mice at the onset of puberty. Expression of androgen receptor (AR) and oestrogen receptor alpha (ERα) mRNA and protein was reduced in skeletal muscles of male and female STAT5B−/− mice, respectively. Loss of STAT5B abolished the sexually dimorphic expression of myostatin protein and Igf1, Ar, Erα, suppressor of cytokine signalling 2 (Socs2), and cytokine-inducible SH2-containing protein (Cis) mRNA in skeletal muscle.ConclusionsSTAT5B appears to mediate GH signalling in skeletal muscles of male mice at all ages, but only until puberty in female mice. STAT5B also appears to mediate the actions of androgens and oestrogens in both male and female mice, but sexually dimorphic growth persists in STAT5B−/− mice.

Beneficial alterations in body composition, physical performance, oxidative stress, inflammatory markers, and adipocytokines induced by long-term high-intensity interval training in an aged rat model

Sarcopenia is associated with loss of muscle mass and function as well as oxidative stress, chronic low-grade inflammatory status, and adipocytokine dysfunction. It has been reported that sarcopenia can be attenuated by exercise training. The purpose of this study was to evaluate whether long-term high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) protocols could differentially modulate changes in body composition, physical performance, inflammatory parameters, and adipocytokines in fat tissues and serum, as well as oxidative parameters and insulin-like growth factor 1 (IGF-1) levels in skeletal muscle tissue of aged rats. Middle-aged (18-month-old) female Sprague Dawley rats (n = 36) were subjected to 8 months of MICT (26-m MICT) or HIIT (26-m HIIT) treadmill training (45 min, 5 times per week), and the results were compared with those of age-matched sedentary controls (26-m SED); 8-month-old (8-m SED) and 18-month-old (18-m SED) rats served as aging sedentary controls. Body composition parameters; physical performance; serum and skeletal muscle oxidative stress parameters; levels of IGF-1, a serum and fat tissue inflammatory marker; adipocytokine (leptin, adiponectin) levels; and plasma glucose and lipid metabolism-related parameters were analyzed among the five groups. The percent fat and body fat to lean mass ratio increased as a main effect with age, whereas 26-m HIIT but not 26-m MICT attenuated these alterations. The 26-m HIIT group showed a larger improvement in grip strength compared to that of 26-m MICT, with a similar increase in inclined plane performance, maximum running speed, and exhaustion over time as compared with the 26-m SED group. Notably, the 26-m HIIT group showed lower high-sensitivity C-reactive protein levels and higher IL-10 in serum compared with those of the 26-m SED and 26-m MICT groups. Both exercise protocols promoted increased skeletal muscle IGF-1 and decreased serum IGF-1 and adiponectin relative to those in the 26-m SED group, whereas only 26-m HIIT dampened the age-related decrease in plasma free fatty acids and increased serum leptin, along with providing lower fat tissue leptin as compared with that in the 26-m SED group. Moreover, the 26-m HIIT group showed lower serum and skeletal muscle malonylaldehyde and skeletal muscle 8-hydroxydeoxyguanosine (8-OHdG) levels than those in the 26-m MICT group, albeit similar decreases in serum and skeletal muscle 4-hydroxynonenal and serum 8-OHdG and increases in skeletal muscle superoxide dismutase 2 activity. In conclusion, HIIT initiated late in life exhibited greater beneficial effects in ameliorating aged-related elevations in oxidative stress and inflammation, as well as dysfunction of circulating adipocytokine levels, than a volume-matched MICT program. HIIT may therefore contribute to improvements in body composition and physical performance changes associated with aging.

Progress in the molecular and genetic modification breeding of beef cattle in China.

The studies of beef cattle breeding in China have been greatly improved with the rapid development of the international beef cattle industrialization. The beef cattle breeding technologies have rapidly transformed from traditional breeding to molecular marker-assisted breeding, genomic selection and genetic modification breeding. Hundreds of candidate genes and molecular markers associated with growth, meat quality, reproduction performance and diseases resistance have been identified, and some of them have already been used in cattle breeding. Genes and molecular markers associated with growth and development are focused on the growth hormone, muscle regulatory factors, myostatin and insulin-like growth factors. Meat quality is mediated by fatty acid transport and deposition related signals, calpains and calpain system, muscle regulatory factors and muscle growth regulation pathways. Reproduction performance is regulated by GnRH-FSH-LH, growth differentiation factor 9, prolactin receptor and forkhead box protein O1. Disease resistance is modulated by the major histocompatibility complex gene family, toll-like receptors, mannose-binding lectin and interferon gene signals. In this review, we summarize the most recent progress in beef cattle breeding in marker-assisted selection, genome-wide selection and genetic modification breeding, aiming to provide a reference for further genetic breeding research of beef cattle in China.

An isoflavone enriched diet increases skeletal muscle adaptation in response to physical activity in ovariectomized rats.

This study was to investigate anabolic adaptation of skeletal muscle in response to an isoflavone (ISO) enriched diet, training and their combinations in ovariectomized (OVX) rats. Female Wistar rats were sedentary, performed treadmill uphill running, received ISOs, or a combination of ISOs and running after ovariectomy. Body weight was increased by OVX. Both ISO and training treatment antagonized this increase. The weights of soleus and gastrocnemius muscles were increased only when training and ISOs were combined. In soleus muscle insulin-like growth factor (IGF)-1R, MyoD and Myogenin expressions were only up-regulated by training in Sham groups. However, a stimulation of IGF-1R and MyoD expression could be observed when ISOs and training were combined. In gastrocnemius muscle MyoD and Myogenin expressions were stimulated by either training or ISOs. Additive effects were detected when combining the two interventions. Our results indicate that the combination of ISOs and exercise is more efficient in increasing relative skeletal muscle mass and the expression of molecular markers related to anabolic adaptation in the skeletal muscle of female rats.

Embryonic-only arsenic exposure in killifish (Fundulus heteroclitus) reduces growth and alters muscle IGF levels one year later

Arsenic is a contaminant of drinking water and crops in many parts of the world. Epidemiological studies have shown that arsenic exposure is linked to decreased birth weight, weight gain, and proper skeletal muscle function. The goal of this study was to use killifish (Fundulus heteroclitus) as a model to determine the long-term effects of embryonic-only arsenic exposure on muscle growth and the insulin-like growth factor (IGF) pathway. Killifish embryos were exposed to 0, 50, 200 or 800ppb AsIII from fertilization until hatching. Juvenile fish were reared in clean water and muscle samples were collected at 16, 28, 40 and 52 weeks of age. There were significant reductions in condition factors, ranging from 12 to 17%, in the fish exposed to arsenic at 16, 28 and 40 weeks of age. However, by 52 weeks, no significant changes in condition factors were seen. Alterations in IGF-1R and IGF-1 levels were assessed as a potential mechanism by which growth was reduced. While there no changes in hepatic IGF-1 transcripts, skeletal muscle cells can also produce their own IGF-1 and/or alter IGF-1 receptor levels to help enhance growth. After a 200 and 800ppb embryonic exposure, fish grown in clean water for 16 weeks had IGF-1R transcripts that were 2.8-fold and 2-fold greater, respectively, than unexposed fish. Through 40 weeks of age, IGF1-R remained elevated in the 200ppb and 800ppb embryonic exposure groups by 1.8–3.9-fold, while at 52 weeks of age, IGF-1R levels were still significantly increased in the 800ppb exposure group. Skeletal muscle IGF-1 transcripts were also significantly increased by 1.9–5.1 fold through the 52 weeks of grow-out in clean by water in the 800ppb embryonic exposure group. Based on these results, embryonic arsenic exposure has long-term effects in that it reduces growth and increases both IGF-1 and IGF-1R levels in skeletal muscle even 1year after the exposure has ended.

Smooth Muscle Insulin-Like Growth Factor-1 Mediates Hypoxia-Induced Pulmonary Hypertension in Neonatal Mice.

Insulin-like growth factor (IGF)-1 is a potent mitogen of vascular smooth muscle cells (SMCs), but its role in pulmonary vascular remodeling associated with pulmonary hypertension (PH) is not clear. In an earlier study, we implicated IGF-1 in the pathogenesis of hypoxia-induced PH in neonatal mice. In this study, we hypothesized that hypoxia-induced up-regulation of IGF-1 in vascular smooth muscle is directly responsible for pulmonary vascular remodeling and PH. We studied neonatal and adult mice with smooth muscle-specific deletion of IGF-1 and also used an inhibitor of IGF-1 receptor (IGF-1R), OSI-906, in neonatal mice. We found that, in neonatal mice, SMC-specific deletion of IGF-1 or IGF-1R inhibition with OSI-906 attenuated hypoxia-induced pulmonary vascular remodeling in small arteries, right ventricular hypertrophy, and right ventricular systolic pressure. Pulmonary arterial SMCs from IGF-1-deleted mice or after OSI-906 treatment exhibited reduced proliferative potential. However, in adult mice, smooth muscle-specific deletion of IGF-1 had no effect on hypoxia-induced PH. Our data suggest that vascular smooth muscle-derived IGF-1 plays a critical role in hypoxia-induced PH in neonatal mice but not in adult mice. We speculate that the IGF-1/IGF-1R axis is important in pathogenesis of PH in the developing lung and may be amenable to therapeutic manipulation in this age group.

L-Leucine Increases Skeletal Muscle IGF-1 but Does Not Differentially Increase Akt/mTORC1 Signaling and Serum IGF-1 Compared to Ursolic Acid in Response to Resistance Exercise in Resistance-Trained Men

Objective: Ursolic acid administration following resistance exercise increases mammalian target of rapamycin complex 1 (mTORC1) activity and skeletal muscle IGF-1 concentration in murines in a manner similar to l-leucine yet remains unexamined in humans. This study examined serum and skeletal muscle insulin-like growth factor-1 (IGF-1) and Akt/mTORC1 signaling activity following ingestion of either ursolic acid or l-leucine immediately after resistance exercise.Methods: Nine resistance-trained men performed 3 lower-body resistance exercise sessions involving 4 sets of 8–10 repetitions at 75%–80% one repetition maximum (1-RM) on the angled leg press and knee extension exercises. Immediately following each session, participants orally ingested 3 g cellulose placebo (PLC), l-leucine (LEU), or ursolic acid (UA). Blood samples were obtained pre-exercise and at 0.5, 2, and 6 hours postexercise. Muscle biopsies were obtained pre-exercise and at 2 and 6 hours postexercise.Results: Plasma leucine increased in LEU at 2 hours postexercise compared to PLC (p = 0.04). Plasma ursolic acid increased in UA at 2 h and 6 hours postexercise compared to PLC and LEU (p < 0.003). No significant differences were observed for serum insulin (p = 0.98) and IGF-1 (p = 0.99) or skeletal muscle IGF-1 receptor (IGF-1R; p = 0.84), Akt (p = 0.55), mTOR (p = 0.09), and p70S6K (p = 0.98). Skeletal muscle IGF-1 was significantly increased in LEU at 2 hours postexercise (p = 0.03) and 6 hours postexercise (p = 0.04) compared to PLC and UA.Conclusion: Three grams of l-leucine and ursolic acid had no effect on Akt/mTORC1 signaling or serum insulin or IGF-1; however, l-leucine increased skeletal muscle IGF-1 concentration in resistance-trained men.

Long-pulse gastric electrical stimulation protects interstitial cells of Cajal in diabetic rats via IGF-1 signaling pathway.

To investigate the effects of different parameters of gastric electrical stimulation (GES) on interstitial cells of Cajal (ICCs) and changes in the insulin-like growth factor 1 (IGF-1) signal pathway in streptozotocin-induced diabetic rats. Male rats were randomized into control, diabetic (DM), diabetic with sham GES (DM + SGES), diabetic with GES1 (5.5 cpm, 100 ms, 4 mA) (DM + GES1), diabetic with GES2 (5.5 cpm, 300 ms, 4 mA) (DM + GES2) and diabetic with GES3 (5.5 cpm, 550 ms, 2 mA) (DM + GES3) groups. The expression levels of c-kit, M-SCF and IGF-1 receptors were evaluated in the gastric antrum using Western blot analysis. The distribution of ICCs was observed using immunolabeling for c-kit, while smooth muscle cells and IGF-1 receptors were identified using α-SMA and IGF-1R antibodies. Serum level of IGF-1 was tested using enzyme-linked immunosorbent assay. Gastric emptying was delayed in the DM group but improved in all GES groups, especially in the GES2 group. The expression levels of c-kit, M-SCF and IGF-1R were decreased in the DM group but increased in all GES groups. More ICCs (c-kit(+)) and smooth muscle cells (α-SMA(+)/IGF-1R(+)) were observed in all GES groups than in the DM group. The average level of IGF-1 in the DM group was markedly decreased, but it was up-regulated in all GES groups, especially in the GES2 group. The results suggest that long-pulse GES promotes the regeneration of ICCs. The IGF-1 signaling pathway might be involved in the mechanism underlying this process, which results in improved gastric emptying.

Effect of the Muscular Strength Exercise and Massage on Muscle Injury Marker and IGF-1

This experiment is to identify the effect of aid combined with strength exercise and massage affecting muscle injury marker and insulin-like growth factor: IGF-1. Therefore, there were Experimental Group (EG) and Control Group (CG) to identify the effect of the experimental aid. Each aided for 60 minutes, 40 minutes of strength exercise and 20 minutes of massage program, total 24 strength exercises, 3 times a week, for 8 weeks. Through this process we could see there is interactive effect on ammonia, phosphorus, creatine kinase, and lactate dehydrogenase, which are muscle injury markers. There is also interactive effect on IGF-1, which is insulin-like growth factor. As a result, aid combined with strength exercise and massage has a positive effect on muscle injury marker and IGF-1.

The aromatic amino acid tryptophan stimulates skeletal muscle IGF1/p70s6k/mTor signaling in vivo and the expression of myogenic genes in vitro

ObjectivesNutrition plays a key role in the maintenance of muscle and bone mass, and dietary protein deficiency has in particular been associated with catabolism of both muscle and bone tissue. One mechanism thought to link protein deficiency with loss of muscle mass is deficiency in specific amino acids that play a role in muscle metabolism. The aim of this study was to test the hypothesis that the essential amino acid tryptophan, and its metabolite kynurenine, might directly affect muscle metabolism in the setting of protein deficiency. MethodsAdult mice (12 mo) were fed a normal diet (18% protein), as well as diets with low protein (8%) supplemented with increasing concentrations (50, 100, and 200 uM) of kynurenine (Kyn) or with tryptophan (Trp; 1.5 mM) for 8 weeks. Myoprogenitor cells were also treated with Trp and Kyn in vitro to determine their effects on cell proliferation and expression of myogenic differentiation markers. ResultsAll mice on the low-protein diets weighed less than the group fed normal protein (18%). Lean mass measured by dual-energy X-ray absorptiometry was lowest in mice on the high Kyn diet, whereas percent lean mass was highest in mice receiving Trp supplementation and percent body fat was lowest in mice receiving Trp. Enzyme-linked immunosorbent assays showed significant increases in skeletal muscle insulin-like growth factor-1, leptin, and the myostatin antagonist follistatin with Trp supplementation. mRNA microarray and gene pathway analysis performed on muscle samples demonstrate that mTor/eif4/p70s6k pathway molecules are significantly up-regulated in muscles from mice on Kyn and Trp supplementation. In vitro, neither amino acid affected proliferation of myoprogenitors, but Trp increased the expression of the myogenic markers MyoD, myogenin, and myosin heavy chain. ConclusionThese findings suggest that dietary amino acids can directly affect molecular signaling in skeletal muscle, further indicating that dietary manipulation with specific amino acids could potentially attenuate muscle loss with dietary protein deficiency.

Hyperglycemia Inhibits Recovery From Disuse-Induced Skeletal Muscle Atrophy in Rats

The purpose of this study was to evaluate the effects of hyperglycemia on skeletal muscle recovery following disuse-induced muscle atrophy in rats. Wistar rats were grouped as streptozotocin-induced diabetic rats and non-diabetic rats. Both ankle joints of each rat were immobilized to induce atrophy of the gastrocnemius muscles. After two weeks of immobilization and an additional two weeks of recovery, tail blood and gastrocnemius muscles were isolated. Serial cross sections of muscles were stained for myosin ATPase (pH 4.5) and alkaline phosphatase activity. Serum insulin and muscle insulin-like growth factor-1 (IGF-1) levels were also measured. Serum insulin levels were significantly reduced in the diabetic rats compared to the non-diabetic controls. The diameters of type I, IIa, and IIb myofibers and capillary-to-myofiber ratio in the isolated muscle tissue were decreased after immobilization in both treatments. During the recovery period, these parameters were restored in the non-diabetic rats, but not in the diabetic rats. In addition, muscle IGF-1 levels after recovery increased significantly in the non-diabetic rats, but not in the diabetic rats. We conclude that decreased levels of insulin and IGF-1 and impairment of angiogenesis associated with diabetes might be partly responsible for the inhibition of regrowth in diabetic muscle.

Polyethylene glycol-coupled IGF1 delays motor function defects in a mouse model of spinal muscular atrophy with respiratory distress type 1

Spinal muscular atrophy with respiratory distress type 1 is a neuromuscular disorder characterized by progressive weakness and atrophy of the diaphragm and skeletal muscles, leading to death in childhood. No effective treatment is available. The neuromuscular degeneration (Nmd(2J)) mouse shares a crucial mutation in the immunoglobulin mu-binding protein 2 gene (Ighmbp2) with spinal muscular atrophy with respiratory distress type 1 patients and also displays some basic features of the human disease. This model serves as a promising tool in understanding the complex mechanisms of the disease and in exploring novel treatment modalities such as insulin-like growth factor 1 (IGF1) which supports myogenic and neurogenic survival and stimulates differentiation during development. Here we investigated the treatment effects with polyethylene glycol-coupled IGF1 and its mechanisms of action in neurons and muscles. Polyethylene glycol-coupled IGF1 was applied subcutaneously every second day from post-natal Day 14 to post-natal Day 42 and the outcome was assessed by morphology, electromyography, and molecular studies. We found reduced IGF1 serum levels in Nmd(2J) mice 2 weeks after birth, which was normalized by polyethylene glycol-coupled IGF1 treatment. Nmd(2J) mice showed marked neurogenic muscle fibre atrophy in the gastrocnemius muscle and polyethylene glycol-coupled IGF1 treatment resulted in muscle fibre hypertrophy and slowed fibre degeneration along with significantly higher numbers of functionally active axonal sprouts. In the diaphragm with predominant myogenic changes a profound protection from muscle fibre degeneration was observed under treatment. No effects of polyethylene glycol-coupled IGF1 were monitored at the level of motor neuron survival. The beneficial effects of polyethylene glycol-coupled IGF1 corresponded to a marked activation of the IGF1 receptor, resulting in enhanced phosphorylation of Akt (protein kinase B) and the ribosomal protein S6 kinase in striated muscles and spinal cord from Nmd(2J) mice. Based on these findings, polyethylene glycol-coupled IGF1 may hold promise as a candidate for future treatment trials in human patients with spinal muscular atrophy with respiratory distress type 1.

Gene expression profile of IGF1 and MSTN mRNA and their correlation with carcass traits in different breeds of geese at 70 d of age

1. The expression of insulin-like growth factor-1 (IGF1) and myostatin (MSTN) mRNA in breast and leg muscle was quantified in 70-d-old Taihu and Wanxi geese by using a Multiplex Competitive Fluorescent–PCR method and the correlations between mRNA levels and carcass traits were analysed.2. IGF1 mRNA expression in breast muscle in Taihu geese was significantly higher than that in Wanxi geese and the MSTN mRNA level in leg muscle in Taihu geese was significantly higher than that in Wanxi geese.3. There was no significant difference in breast muscle MSTN or leg muscle IGF1 mRNA expression between the two breeds.4. Within the same breed, the IGF1 mRNA expression in leg muscle of male geese was significantly higher than that in female geese, and MSTN mRNA expression in leg muscle was significantly higher than that in breast muscle.5. There was no difference in the IGF1 mRNA expression between tissues.6. There was a positive correlation between IGF1 mRNA and MSTN mRNA and a negative correlation between IGF1 mRNA expression of breast muscle and leg muscle ratio.7. In Wanxi geese, MSTN mRNA expression in leg muscle was negatively associated with body weight and leg muscle weight.

Early changes of muscle insulin‐like growth factor‐1 and myostatin gene expression in gastric cancer patients

Cachexia increases morbidity and mortality of cancer patients. The progressive loss of muscle mass negatively affects physical function and quality of life. We previously showed reduced muscle insulin-like growth factor-1 (IGF-1) expression and enhanced myostatin signaling in tumor-bearing animals. This study was aimed at investigating whether similar perturbations occur in gastric cancer patients. Early perturbations of myostatin and IGF-1 signaling (including the expression of muscle-specific ubiquitin ligases) were investigated in 16 gastric cancer patients and in 6 controls by analyzing muscle mRNA expression with semiquantitative reverse transcriptase polymerase chain reaction (PCR) and real-time PCR. In gastric cancer patients, muscle mRNA levels for IGF-1, myostatin, and atrogin-1 were reduced irrespective of weight loss (≤5% or >5%), whereas MuRF1 expression was unchanged. IGF-1 and myostatin mRNA levels are downregulated in gastric cancer patients who have minimal or no weight loss. These early alterations are particularly relevant in order to devise preventive and therapeutic strategies for cancer cachexia.