Stimulation of muscle protein synthesis by somatotropin in pigs is independent of the somatotropin-induced increase in circulating insulin (original) (raw)
Related papers
American Journal of Physiology-endocrinology and Metabolism, 2008
Wilson FA, Suryawan A, Orellana RA, Nguyen HV, Jeyapalan AS, Gazzaneo MC, Davis TA. Fed levels of amino acids are required for the somatotropin-induced increase in muscle protein synthesis. Chronic somatotropin (pST) treatment in pigs increases muscle protein synthesis and circulating insulin, a known promoter of protein synthesis. Previously, we showed that the pST-mediated rise in insulin could not account for the pST-induced increase in muscle protein synthesis when amino acids were maintained at fasting levels. This study aimed to determine whether the pST-induced increase in insulin promotes skeletal muscle protein synthesis when amino acids are provided at fed levels and whether the response is associated with enhanced translation initiation factor activation. Growing pigs were treated with pST (0 or 180 g ⅐ kg Ϫ1 ⅐ day Ϫ1 ) for 7 days, and then pancreaticglucose-amino acid clamps were performed. Amino acids were raised to fed levels in the presence of either fasted or fed insulin concentrations; glucose was maintained at fasting throughout. Muscle protein synthesis was increased by pST treatment and by amino acids (with or without insulin) (P Ͻ 0.001). In pST-treated pigs, fed, but not fasting, amino acid concentrations further increased muscle protein synthesis rates irrespective of insulin level (P Ͻ 0.02). Fed amino acids, with or without raised insulin concentrations, increased the phosphorylation of S6 kinase (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1), decreased inactive 4EBP1 ⅐ eIF4E complex association, and increased active eIF4E ⅐ eIF4G complex formation (P Ͻ 0.02). pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of muscle protein synthesis requires fed amino acid levels, but not fed insulin levels.
Regulation of translation initiation by insulin and amino acids in skeletal muscle of neonatal pigs
American Journal of Physiology - Endocrinology And Metabolism, 2003
Previous studies have shown that intravenous infusion of insulin and/or amino acids reproduces the feeding-induced stimulation of muscle protein synthesis in neonates and that insulin and amino acids act independently to produce this effect. The goal of the present study was to delineate the regulatory roles of insulin and amino acids on muscle protein synthesis in neonates by examining translational control mechanisms, specifically the eukaryotic translation initiation factors (eIFs), which enable coupling of initiator methionyl-tRNAi and mRNA to the 40S ribosomal subunit. Insulin secretion was blocked by somatostatin in fasted 7-day-old pigs ( n = 8–12/group), insulin was infused to achieve plasma levels of ∼0, 2, 6, and 30 μU/ml, and amino acids were clamped at fasting or fed levels or, at the high insulin dose, below fasting. Both insulin and amino acids increased the phosphorylation of ribosomal protein S6 kinase (S6K1) and the eIF4E-binding protein (4E-BP1), decreased the bind...
Somatotropin increases protein balance by lowering body protein degradation in fed, growing pigs
American Journal of …, 2000
Somatotropin increases protein balance by lowering body protein degradation in fed, growing pigs. Am. J. Physiol. Endocrinol. Metab. 278: E477-E483, 2000.-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 (ϳ20 kg) growing swine were treated with porcine ST (150 µg • kg Ϫ1 • day Ϫ1 , n ϭ 6) or diluent (n ϭ 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 (ϩ100%) and insulin (ϩ125%) concentrations and decreased plasma urea nitrogen concentrations (Ϫ53%). ST-treated pigs had lower leucine R a (Ϫ33%), leucine oxidation (Ϫ63%), and urea production (Ϫ70%). 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.
American Journal of …, 2002
hanced protein synthesis in skeletal muscle after ingestion of a balanced meal in postabsorptive rats is mimicked by oral leucine administration. To assess the contribution of insulin to the protein synthetic response to leucine, food-deprived (18 h) male rats (ϳ200 g) were intravenously administered a primed-constant infusion of somatostatin (60 g ϩ 3 g ⅐ kg Ϫ1 ⅐ h Ϫ1) or vehicle beginning 1 h before administration of leucine (1.35 g L-leucine/kg) or saline (control). Rats were killed 15, 30, 45, 60, or 120 min after leucine administration. Compared with controls, serum insulin concentrations were elevated between 15 and 45 min after leucine administration but returned to basal values by 60 min. Somatostatin maintained insulin concentrations at basal levels throughout the time course. Protein synthesis was increased between 30 and 60 min, and this effect was blocked by somatostatin. Enhanced assembly of the mRNA cap-binding complex (composed of eukaryotic initiation factors eIF4E and eIF4G) and hyperphosphorylation of the eIF4E-binding protein 1 (4E-BP1), the 70-kDa ribosomal protein S6 kinase (S6K1), and the ribosomal protein S6 (rp S6) were observed as early as 15 min and persisted for at least 60 min. Somatostatin attenuated the leucine-induced changes in 4E-BP1 and S6K1 phosphorylation and completely blocked the change in rp S6 phosphorylation but had no effect on eIF4G ⅐ eIF4E assembly. Overall, the results suggest that the leucine-induced enhancement of protein synthesis and the phosphorylation states of 4E-BP1 and S6K1 are facilitated by the transient increase in serum insulin. In contrast, assembly of the mRNA cap-binding complex occurs independently of increases in insulin and, by itself, is insufficient to stimulate rates of protein synthesis in skeletal muscle after leucine administration. amino acids; eukaryotic initiation factors; rats; somatostatin; time course CONSUMPTION OF A PROTEIN-CONTAINING MEAL enhances the fractional rate of synthesis of total mixed proteins in skeletal muscle. The feeding-induced stimulation of
American Journal of Physiology-Endocrinology and Metabolism, 2007
Insulin and amino acids act independently to stimulate protein synthesis in skeletal muscle of neonatal pigs, and the responses decrease with development. The purpose of this study was to compare the separate effects of fed levels of INS and AA on the activation of signaling components leading to translation initiation and how these responses change with development. Overnight-fasted 6- ( n = 4/group) and 26-day-old ( n = 6/ group) pigs were studied during 1) euinsulinemic-euglycemiceuaminoacidemic conditions (controls), 2) euinsulinemic-euglycemichyperaminoacidemic clamps (AA), and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps (INS). INS, but not AA, increased the phosphorylation of protein kinase B (PKB) and tuberous sclerosis 2 (TSC2). Both INS and AA increased protein synthesis and the phosphorylation of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase-1, and eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1), and these responses were higher...
The Journal of Nutrition, 2021
Background Nutrition administered as intermittent bolus feeds rather than continuously promotes greater protein synthesis rates in skeletal muscle and enhances lean growth in a neonatal piglet model. The molecular mechanisms responsible remain unclear. Objectives We aimed to identify the insulin- and/or amino acid-signaling components involved in the enhanced stimulation of skeletal muscle by intermittent bolus compared to continuous feeding in neonatal pigs born at term. Methods Term piglets (2–3 days old) were fed equal amounts of sow milk replacer [12.8 g protein and 155 kcal/(kg body weight · d)] by orogastric tube as intermittent bolus meals every 4 hours (INT) or by continuous infusion (CTS). After 21 days, gastrocnemius muscle samples were collected from CTS, INT-0 (before a meal), and INT-60 (60 minutes after a meal) groups (n = 6/group). Insulin- and amino acid-signaling components relevant to mechanistic target of rapamycin complex (mTORC) 1 activation and protein translat...
Nutrient uptake by the hindlimb of growing pigs treated with porcine somatotropin and insulin
The Journal of …, 1995
The shift in nutrient partitioning induced by porcine somatotropin (pST) is accompanied by a decrease in insulin sensitivity for whole-body glucose uptake. The relative contribution of metabolic changes in the hindlimb was investigated in eight pigs (55 kg) that had received recombinant pST (120 ng/kg) or excipient (control) for 7 d. Uptake of metabolites by the hindlimb was measured under basal conditions and during hyperinsulinemic-euglycemic clamps at low [14 ng/ (kg.min)] and high [360 ng/(kg-min)] insulin infusion rates. Dextrose infusion rate required to maintain euglycemia was used as an index of whole-body glucose uptake in response to exogenous insulin. Effects of pST on hindlimb and whole-body glucose uptake were evident only at physiological levels of insulin (basal and low insulin infusion rate). During the low rate of insulin in fusion, dextrose infusion rate was 79% lower for pSTtreated pigs and glucose uptake by the hindlimb was 59% lower compared with control pigs. The decrease in glucose uptake by the hindlimb was entirely accounted for by the estimated reduction in glucose utilization by adipose tissue of the hindlimb. Glucose:oxygen quo tients were reduced during basal (57%) and low insulin infusion (63%) with pST treatment, indicating a change in the pattern of substrate utilization. This is consistent with the concept that pST directs nutrients away from adipose and towards muscle growth by altering the re sponse of tissues to homeostatic signals such as in sulin. J. Nutr. 125: 125-135, 1995.
Insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonatal pigs
American Journal of Physiology - Endocrinology And Metabolism, 2002
Infusion of physiological levels of insulin and/or amino acids reproduces the feeding-induced stimulation of muscle protein synthesis in neonates. To determine whether insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonates, insulin secretion was blocked with somatostatin in fasted 7-day-old pigs ( n = 8–12/group) while glucose and glucagon were maintained at fasting levels and insulin was infused to simulate either less than fasting, fasting, intermediate, or fed insulin levels. At each dose of insulin, amino acids were clamped at either the fasting or fed level; at the highest insulin dose, amino acids were also reduced to less than fasting levels. Skeletal muscle protein synthesis was measured using a flooding dose ofl-[4-3H]phenylalanine. Hyperinsulinemia increased protein synthesis in skeletal muscle during hypoaminoacidemia and euaminoacidemia. Hyperaminoacidemia increased muscle protein synthesis during hypoinsulinemia and euinsulinemia. ...
Response of skeletal muscle protein synthesis to insulin in suckling pigs decreases with development
American Journal of Physiology-Endocrinology and Metabolism, 1998
The elevated rate of muscle protein deposition in the neonate is largely due to an enhanced stimulation of skeletal muscle protein synthesis by feeding. To examine the role of insulin in this response, hyperinsulinemic-euglycemic-amino acid clamps were performed in 7- and 26-day-old pigs. Pigs were infused with 0, 30, 100, or 1,000 ng ⋅ kg−0.66 ⋅ min−1of insulin to mimic the plasma insulin levels observed under fasted, fed, refed, and supraphysiological conditions, respectively. Whole body amino acid disposal was determined from the rate of infusion of an amino acid mixture necessary to maintain plasma essential amino acid concentrations near their basal fasting levels. A flooding dose ofl-[4-3H]phenylalanine was used to measure skeletal muscle protein synthesis. Whole body amino acid disposal increased progressively as the insulin infusion rate increased, and this response was greater in 7- than in 26-day-old pigs. Skeletal muscle protein synthesis was stimulated by insulin, and th...