Biomedical subjects

M L Fiorotto

Publications and source records attributed to M L Fiorotto.

At least 19 recordsLinked to original sources

PubMed2004

A new plasmid-mediated approach to supplement somatotropin production in pigs.

Tremendous progress has been made in the identification of the stimulatory molecules that regulate growth, the mechanisms of action, and the potential application of these molecules for livestock production. A parallel and significant effort is now focused on the discovery and development of economically feasible gene delivery technologies. Plasmid-mediated GHRH gene transfer has emerged as an excellent candidate for agricultural applications to optimize production and animal welfare. We have engineered a GHRH-expressing plasmid that is efficiently expressed in skeletal muscle following intramuscular injection enhanced by electroporation. The GHRH is synthesized in the injected muscle, from which it is secreted to circulate and stimulate normal pituitary GH production and release. Young pigs directly injected with as little as 0.1 mg of a GHRH-expressing plasmid had greater (P < 0.01) weight gain than controls, and a increase (P < 0.05) in fat-free mass. We also have demonstrated that the offspring of gilts injected intramuscularly at d 85 of gestation with a GHRH-expressing plasmid have optimized growth characteristics due to both improved intrauterine weight gain and enhanced maternal lactation performance. Thus, the piglets from treated gilts were larger at birth and weaning compared to controls and reached market weight earlier (P < 0.001). Additionally, pituitaries collected from this group contained an increased number of somatotrophs and lactotrophs (P < 0.001) at birth and at 100 kg. An additional advantage of administering the GHRH plasmid to the gilt compared with the administration of growth-promoting agents to the individual adult animal is a substantial decrease in offspring morbidity and mortality (P < 0.01), which has always represented a major economic loss for the swine industry.

Animals↗

PubMed2001

Long-term insulin-like growth factor-I expression in skeletal muscles attenuates the enhanced in vitro proliferation ability of the resident satellite cells in transgenic mice.

Insulin-like growth factor-I (IGF-I) overexpression for 1-month in mouse skeletal muscle increases satellite cell proliferation potential. However, it is unknown whether this beneficial enhancement by IGF-I expression would persist over a longer-term duration in aged mice. This is an important issue to address if a prolonged course of IGF-I is to be used clinically in muscle-wasting conditions where satellite cells may become limiting. Using the IGF-I transgenic (IGF-I Tg) mouse that selectively expresses the IGF-I transgene in striated muscles, we found that 18-months of continuous IGF-I overexpression led to a loss in the enhanced in vitro proliferative capacity of satellite cells from Tg skeletal muscles. Also 18-month-old IGF-I Tg satellite cells lost the enhanced BrdU incorporation, greater pRb and Akt phosphorylations, and decreased p27(Kip1) levels initially observed in cells from 1-month-old IGF-I Tg mice. The levels of those biochemical markers reverted to similar values seen in the 18-months WT littermates. These findings, therefore, suggest that there is no further beneficial effect on enhancing satellite cell proliferation ability with persistent long-term expression of IGF-I in skeletal muscles of these transgenic mice.

Aging↗

PubMed2001

Differential effects of insulin on peripheral and visceral tissue protein synthesis in neonatal pigs.

We recently demonstrated in neonatal pigs that, with amino acids and glucose maintained at fasting levels, the stimulation of protein synthesis in longissimus dorsi muscle with feeding can be reproduced by a physiological rise in insulin alone. In the current report, we determine whether the response of protein synthesis to insulin in the neonatal pig is 1) present in muscles of different fiber types, 2) proportional in myofibrillar and sarcoplasmic proteins, 3) associated with increased translational efficiency and ribosome number, and 4) present in other peripheral tissues and in viscera. Hyperinsulinemic-euglycemic-amino acid clamps were performed in 7- and 26-day-old pigs infused with 0, 30, 100, or 1,000 ng. kg(-0.66). min(-1) of insulin to reproduce insulin levels present in fasted, fed, refed, and supraphysiological conditions, respectively. Tissue protein synthesis was measured using a flooding dose of L-[4-(3)H]phenylalanine. Insulin increased protein synthesis in gastrocnemius muscle and, to a lesser degree, masseter muscle. The degree of stimulation of protein synthesis by insulin was similar in myofibrillar and sarcoplasmic proteins. Insulin increased translational efficiency but had no effect on ribosome number in muscle. All of these insulin-induced changes in muscle protein synthesis decreased with age. Insulin also stimulated protein synthesis in cardiac muscle and skin but not in liver, intestine, spleen, pancreas, or kidney. The results support the hypothesis that insulin mediates the feeding-induced stimulation of myofibrillar and sarcoplasmic protein synthesis in muscles of different fiber types in the neonate by increasing the efficiency of translation. However, insulin does not appear to be involved in the feeding-induced stimulation of protein synthesis in visceral tissues. Thus different mechanisms regulate the growth of peripheral and visceral tissues in the neonate.

Amino Acids↗

PubMed2000

Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway.

Interest is growing in methods to extend replicative life span of non-immortalized stem cells. Using the insulin-like growth factor I (IGF-I) transgenic mouse in which the IGF-I transgene is expressed during skeletal muscle development and maturation prior to isolation and during culture of satellite cells (the myogenic stem cells of mature skeletal muscle fibers) as a model system, we elucidated the underlying molecular mechanisms of IGF-I-mediated enhancement of proliferative potential of these cells. Satellite cells from IGF-I transgenic muscles achieved at least five additional population doublings above the maximum that was attained by wild type satellite cells. This IGF-I-induced increase in proliferative potential was mediated via activation of the phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated protein kinase activity, facilitating G(1)/S cell cycle progression via a down-regulation of p27(Kip1). Adenovirally mediated ectopic overexpression of p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A protein abundance, thereby implicating an important role for p27(Kip1) in promoting satellite cell senescence. These observations provide a more complete dissection of molecular events by which increased local expression of a growth factor in mature skeletal muscle fibers extends replicative life span of primary stem cells than previously known.

Animals↗

PubMed2000

Protein nutrition of the neonate.

The period of growth and development between birth and weaning is crucial for the long-term well-being of the organism. Protein deposition is very rapid, is achieved with a high nutritional efficiency, and is accompanied by marked differences in the growth rates of individual tissues and a series of maturational processes. These important aspects of development occur while the neonate is consuming a single and highly-specific food source, milk. Surprisingly, although there is a clear relationship between the nutrient density of milk and the growth rate of its recipient, this relationship does not apply to the overall amino acid composition of mixed milk proteins. Some amino acids, notably glycine and arginine, are supplied in milk in quantities that are much less than the needs of the neonate. The milk-fed neonate is therefore capable of carrying out a tightly-regulated transfer of N from amino acids in excess to those that are deficient. The rapid growth of the neonate is supported by a high rate of tissue protein synthesis. This process appears to be activated by the consumption of the first meals of colostrum. Recent research has identified that skeletal muscle and the brain are specifically responsive to an unidentified factor in colostrum. Following the initial anabolic response the rate of protein synthesis in some tissues, notably muscle, falls from birth to weaning. This decrease reflects a progressively smaller anabolic response to nutrient intake, which not only involves an overall fall in the capacity for protein synthesis, but also in responses to insulin and amino acids. The study of growth and protein metabolism, and their regulation in the neonate is not only important for pediatrics, but may provide important pointers to more general aspects of regulation that could be applied to the nutrition of the mature animal.

Amino Acids↗

PubMed2000

Somatotropin increases protein balance by lowering body protein degradation in fed, growing pigs.

Somatotropin (ST) administration enhances protein deposition in well-nourished, growing animals. To determine whether the anabolic effect is due to an increase in protein synthesis or a decrease in proteolysis, pair-fed, weight-matched ( approximately 20 kg) growing swine were treated with porcine ST (150 microg. kg(-1). day(-1), n = 6) or diluent (n = 6) for 7 days. Whole body leucine appearance (R(a)), nonoxidative leucine disposal (NOLD), urea production, and leucine oxidation, as well as tissue protein synthesis (K(s)), were determined in the fed steady state using primed continuous infusions of [(13)C]leucine, [(13)C]bicarbonate, and [(15)N(2)]urea. ST treatment increased the efficiency with which the diet was used for growth. ST treatment also increased plasma insulin-like growth factor I (+100%) and insulin (+125%) concentrations and decreased plasma urea nitrogen concentrations (-53%). ST-treated pigs had lower leucine R(a) (-33%), leucine oxidation (-63%), and urea production (-70%). However, ST treatment altered neither NOLD nor K(s) in the longissimus dorsi, semitendinosus, or gastrocnemius muscles, liver, or jejunum. The results suggest that in the fed state, ST treatment of growing swine increases protein deposition primarily through a suppression of protein degradation and amino acid catabolism rather than a stimulation of protein synthesis.

Animals↗

PubMed2000

Regulation of myofibrillar protein turnover during maturation in normal and undernourished rat pups.

The study tested the hypothesis that a higher rate of myofibrillar than sarcoplasmic protein synthesis is responsible for the rapid postdifferentiation accumulation of myofibrils and that an inadequate nutrient intake will compromise primarily myofibrillar protein synthesis. Myofibrillar (total and individual) and sarcoplasmic protein synthesis, accretion, and degradation rates were measured in vivo in well-nourished (C) rat pups at 6, 15, and 28 days of age and compared at 6 and 15 days of age with pups undernourished (UN) from birth. In 6-day-old C pups, a higher myofibrillar than sarcoplasmic protein synthesis rate accounted for the greater deposition of myofibrillar than sarcoplasmic proteins. The fractional synthesis rates of both protein compartments decreased with age, but to a greater degree for myofibrillar proteins (-54 vs. -42%). These decreases in synthesis rates were partially offset by reductions in degradation rates, and from 15 days, myofibrillar and sarcoplasmic proteins were deposited in constant proportion to one another. Undernutrition reduced both myofibrillar and sarcoplasmic protein synthesis rates, and the effect was greater at 6 (-25%) than 15 days (-15%). Decreases in their respective degradation rates minimized the effect of undernutrition on sarcoplasmic protein accretion from 4 to 8 days and on myofibrillar proteins from 13 to 17 days. Although these adaptations in protein turnover reduced overall growth of muscle mass, they mitigated the effects of undernutrition on the normal maturational changes in myofibrillar protein concentration.

Actins↗

PubMed2000

Perinatal ontogeny of brain growth in the domestic pig.

The perinatal development of the brain is highlighted by a growth spurt whose timing varies among species. The growth of the porcine cerebrum was investigated from the third trimester of gestation (70 days postconception) through the first 3.5 weeks of postnatal life (140 days postconception). The shape of the growth curves for cerebrum weight, total protein mass, total cell number (estimated by DNA content), and myelination (estimated by cholesterol accretion) were described. The growth velocity of cerebrum weight had two peaks, one at 90 days and the other at 130 days postconception, whereas that of total protein was greatest from 90 to 130 days postconception, and that of total DNA was greatest between 90 and 110 days and again at 130 days postconception. The growth velocity for total cholesterol continued to increase during the entire period, suggesting that myelination continued after the growth spurts for cells (protein and DNA). The growth velocity patterns observed in these contemporary pigs suggest that this species may be an appropriate model for human brain development, not only in the perinatal pattern of increase in mass of the cerebrum, as established previously, but also with regard to the patterns of cellular development and myelination.

Aging↗

PubMed2000

Nonnutritive factors in colostrum enhance myofibrillar protein synthesis in the newborn Pig.

Colostrum is a complex source of nutrients, immune factors, and bioactive substances consumed by newborn mammals. In previous work, we observed that protein synthesis in the skeletal muscle of newborn piglets is enhanced when they are fed colostrum rather than a nutrient-matched formula devoid of growth factors. To elucidate the mechanisms responsible for this response, we contrasted the fractional rates of sarcoplasmic and myofibrillar protein synthesis of newborn piglets that received only water with those fed for 24 h with colostrum, a nutrient-matched formula, or mature sow's milk. Compared with water, feeding resulted in a 2.5- to 3-fold increase in total skeletal muscle protein synthesis, and this increase was 28% greater in the colostrum-fed than either the formula- or mature milk-fed piglets. Feeding also stimulated muscle ribosome and total polyadenylated RNA accretion. Ribosomal translational efficiency, however, was similar across all fed groups. The greater stimulation of protein synthesis in colostrum-fed pigs was restricted entirely to the myofibrillar protein compartment and was associated with higher ribosome and myosin heavy chain mRNA abundance. Taken together, these data suggest that nonnutritive factors in colostrum enhance ribosomal accretion and muscle-specific gene transcription that, in turn, stimulate specifically the synthesis of myofibrillar proteins in the skeletal musculature of the newborn.

Animals↗

PubMed2000

Protein kinetics in callipyge lambs.

The objectives for this experiment were to determine the effect of the callipyge phenotype on protein kinetics. We studied callipyge and normal lambs (n = 37) at 5, 8, and 11 wk of age (n = 4 to 7/ group) to determine how protein kinetics are altered by this trait. Total protein, DNA, and RNA and calpastatin activity were measured in five skeletal muscles and in the heart, kidneys, and liver, and protein accretion rates were calculated. At 8 wk, the fractional synthesis rates of proteins in these tissues were measured in vivo using a primed, continuous 8-h infusion of [2H5]phenylalanine. Fractional rates of protein degradation were estimated by differences. At 5 wk of age, muscle weights, protein mass, protein:DNA, RNA:DNA, and calpastatin activity were higher (P < .05) for callipyge, and protein mass differences continued to increase through 11 wk. At 8 wk, fractional rates of protein synthesis and degradation were lower (P < .05) in callipyge than in normal lambs. The organs of callipyge lambs exhibited reduced growth at 11 wk. Thus, enhanced muscle growth seems to be maintained in callipyge lambs by reduced protein degradation rather than increased protein synthesis. However, we cannot exclude the possibility that the initial onset of the callipyge condition may be caused by an increase in the fractional rate of protein synthesis.

Animals↗

PubMed1999

Myogenic expression of an injectable protease-resistant growth hormone-releasing hormone augments long-term growth in pigs.

Ectopic expression of a new serum protease-resistant porcine growth hormone-releasing hormone, directed by an injectable muscle-specific synthetic promoter plasmid vector (pSP-HV-GHRH), elicits growth in pigs. A single 10 mg intramuscular injection of pSP-HV-GHRH DNA followed by electroporation in three-week-old piglets elevated serum GHRH levels by twofold to fourfold, enhanced growth hormone secretion, and increased serum insulin-like growth factor-I by threefold to sixfold over control pigs. After 65 days the average body weight of the pigs injected with pSP-HV-GHRH was approximately 37% greater than the placebo-injected controls and resulted in a significant reduction in serum urea concentration, indicating a decrease in amino acid catabolism. Evaluation of body composition indicated a uniform increase in mass, with no organomegaly or associated pathology.

Animals↗

PubMed1999

Transgenic hypersecretion of des(1-3) human insulin-like growth factor I in mouse milk has limited effects on the gastrointestinal tract in suckling pups.

We tested the hypothesis that chronic ingestion of increased concentrations of milk-borne des(1-3) human insulin-like growth factor-I (hIGF-I) stimulates gastrointestinal growth and development in suckling mice. We used a transgenic mouse with targeted, lactation-dependent, overexpression of des(1-3) hIGF-I in the mammary gland (IGF). Pups were suckled (7 pups per litter) from birth by either IGF (n = 3-6 litters) or control (n = 3-5 litters) dams. In IGF and control pups, we measured the growth (protein and DNA content) and protein synthesis rate (3H-phenylalanine incorporation) of gastrointestinal and visceral organs in 4-, 8-, 12-, 16- and 29-d-old pups. Des(1-3) hIGF-I in milk from IGF dams was 40-200-fold higher than mouse IGF in either IGF or control dams, but was not detected in the plasma of pups suckling IGF dams. Small intestinal weight, protein and DNA content at 8 and 16 d were greater in pups suckling IGF dams than control dams; protein synthesis was also greater in IGF pups at 8 d. Total intestinal lactase activity at 8 and 12 d of age tended to be higher (P < 0.10) in IGF than in control pups. Hypersecretion of des(1-3) hIGF-I in milk ingested by suckling mice pups had limited effects on the growth and maturation of the gastrointestinal tract. Moreover, there was little evidence that milk-borne IGF-I is absorbed into the circulation and stimulates visceral organ growth. This study also demonstrates the feasibility of using mammary-specific transgenes to increase the concentration of milk-borne growth factors to examine whether they affect the growth and development of the suckling neonate.

Animals↗

PubMed1999

Local insulin-like growth factor I expression induces physiologic, then pathologic, cardiac hypertrophy in transgenic mice.

In the present study we determined the long-term effects of persistent, local insulin-like growth factor I (IGF-I) expression on cardiac function in the SIS2 transgenic mouse. Cardiac mass/tibial length was increased in SIS2 mice by 10 wk of age; this cardiac hypertrophy became more pronounced later in life. Peak aortic outflow velocity, a correlate of cardiac output, was increased at 10 wk in SIS2 mice but was decreased at 52 wk. 72 wk SIS2 mouse hearts exhibited wide variability in the extent of cardiac hypertrophy and enlargement of individual cardiac myofibers. Sirius red staining revealed increased fibrosis in 72 wk SIS2 hearts. Persistent local IGF-I expression is sufficient to initially induce an analog of physiological cardiac hypertrophy in which peak aortic outflow velocity is increased relative to controls in the absence of any observed detrimental histological changes. However, this hypertrophy progresses to a pathological condition characterized by decreased systolic performance and increased fibrosis. Our results confirm the short-term systolic performance benefit of increased IGF-I, but our demonstration that IGF-I ultimately diminishes systolic performance raises doubt about the therapeutic value of chronic IGF-I administration. Considering these findings, limiting temporal exposure to IGF-I seems the most likely means of delivering IGF-I's potential benefits while avoiding its deleterious side effects.

Animals↗

PubMed1999

Dexamethasone inhibits small intestinal growth via increased protein catabolism in neonatal pigs.

Our objective was to determine how dexamethasone (Dex) affects gastrointestinal protein metabolism and growth in neonatal pigs. Two-day-old pigs were given daily subcutaneous injections of either Dex (1 mg/kg body wt, n = 7) or saline (control, n = 6) for 7 days. In vivo protein synthesis was measured after 7 days with a bolus of [3H]phenylalanine. Tissue protein contents were measured in an initial control group of 2-day-old pigs and in control and Dex pigs after 7 days to estimate protein accretion and degradation. In control pigs, the protein accretion in the ileum was nearly sixfold greater than in the jejunum during the 7-day period. Dex nominally altered stomach growth but completely blocked the accretion of protein and DNA in the jejunum and ileum, with reduced villus height in the ileum. Dex increased the fractional protein degradation rate in the ileum (28%) and decreased the absolute protein synthesis rate in the jejunum and ileum by 17 and 21%, respectively. Dex resulted in a 40% lower total intestinal lactase activity compared with controls via reductions in both specific activity and tissue mass, especially in the ileum. Dex significantly decreased the circulating concentrations of insulin-like growth factor (IGF) I and IGF-binding protein (IGFBP)-1, -2, and -3. However, the tissue abundance of the IGF-I receptor in the stomach and ileum was greater in Dex pigs than controls. Our results suggest that Dex significantly inhibits small intestinal growth via both increased degradation and decreased synthesis of protein. Furthermore, the inhibition of intestinal growth resulted in significantly decreased lactose digestive capacity.

Animals↗

PubMed1999

Aminoacyl-tRNA and tissue free amino acid pools are equilibrated after a flooding dose of phenylalanine.

The flooding dose method, which is used to measure tissue protein synthesis, assumes equilibration of the isotopic labeling between the aminoacyl-tRNA pool and the tissue and blood free amino acid pools. However, this has not been verified for a phenylalanine tracer in an in vivo study. We determined the specific radioactivity of [(3)H]phenylalanine in the aminoacyl-tRNA and the tissue and blood free amino acid pools of skeletal muscle and liver 30 min after administration of a flooding dose of phenylalanine along with [(3)H]phenylalanine. Studies were performed in neonatal pigs in the fasted and refed states and during hyperinsulinemic-euglycemic-amino acid clamps. The results showed that, 30 min after the administration of a flooding dose of phenylalanine, there was equilibration of the specific radioactivity of phenylalanine among the blood, tissue, and tRNA precursor pools. Equilibration of the specific radioactivity of the three precursor pools for protein synthesis occurred in both skeletal muscle and liver. Neither feeding nor insulin status affected the aminoacyl-tRNA specific radioactivity relative to the tissue free amino acid specific radioactivity. The results support the assumption that the tissue free amino acid pool specific radioactivity is a valid measure of the precursor pool specific radioactivity and thus can be used to calculate protein synthesis rates in skeletal muscle and liver when a flooding dose of phenylalanine is administered.

Amino Acids↗

PubMed1998

Roles of insulin and amino acids in the regulation of protein synthesis in the neonate.

Neonates deposit protein at a very high rate and efficiently utilize dietary amino acids for protein deposition. This high efficiency is associated with an elevated stimulation of tissue protein synthesis by feeding. Our recent studies have focused on identification of the factors that mediate this response in the neonate. A positive curvilinear relationship between skeletal muscle protein synthesis and plasma insulin concentration was identified in fasted and fed suckling pigs; the relationship changes with development. To test the specific effects of insulin on protein metabolism in the neonate, a procedure to clamp amino acids, under hyperinsulinemic conditions, was developed. By using this technique, we showed that insulin-stimulated whole-body amino acid disposal is elevated in the neonate, and this response may account for the efficient use of dietary amino acids for protein accretion. More recent studies suggest that the enhanced stimulation of skeletal muscle protein synthesis by feeding in the neonate is primarily insulin mediated; however, the stimulation of liver protein synthesis by feeding seems to be largely a function of amino acid concentration.

Amino Acids↗

PubMed1998

Exogenous growth hormone stimulates somatotropic axis function and growth in neonatal pigs.

We studied the effects of exogenous porcine growth hormone (pGH) administration on circulating insulin-like growth factor I (IGF-I) concentration, IGF-binding proteins (IGFBP), tissue growth, and protein synthesis in neonatal pigs. One-day-old pigs were given daily intramuscular injections of either pGH (1 mg/kg body wt) (n = 6) or saline (n = 5) for 7 days, after which time we measured in vivo protein synthesis using a bolus of [3H]-phenylalanine. Mean plasma pGH concentration in pGH-treated pigs measured on day 7 was 22-fold higher than in controls. The plasma IGF-I concentration in pGH-treated pigs was significantly greater than in controls after 1 day of treatment and plateaued at 285% of control values after 4 days. After 7 days of treatment, plasma IGFBP-3 concentrations and the plasma glucose response to a meal were also greater in pGH-treated than control pigs. pGH treatment significantly increased body weight gain and food conversion efficiency and the protein synthesis rate in several visceral organs. Our results demonstrate that exogenous pGH increases circulating IGF-I and IGFBP-3 concentrations and visceral organ growth in neonatal pigs, suggesting that the somatotrophic axis is functional in the neonate.

Animals↗

PubMed1998

Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy.

This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hypothesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mice overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontransgenic mice from the parent strain (FVB) were divided into four groups (n = 10/group): 1) transgenic, weight-bearing (IGF-I/WB); 2) transgenic, hindlimb unloaded (IGF-I/HU); 3) nontransgenic, weight-bearing (FVB/WB); and 4) nontransgenic, hindlimb unloaded (FVB/HU). HU groups were hindlimb unloaded for 14 days. Body mass was reduced (P < 0.05) after HU in both IGF-I (-9%) and FVB mice (-13%). Contrary to our hypothesis, we found that the relative abundance of mRNA for the endogenous rodent IGF-I (rIGF-I) was unaltered by HU in the gastrocnemius (GAST) muscle of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the GAST and tibialis anterior (TA) muscles of the transgenic mice. Nevertheless, masses of the GAST and TA muscles were reduced (P < 0.05) in both FVB/HU and IGF-I/HU groups compared with FVB/WB and IGF-I/WB groups, respectively, and the percent atrophy in mass of these muscles did not differ between FVB and IGF-I mice. Therefore, skeletal muscle atrophy may not be associated with a reduction of endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that high local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in mice.

Actins↗