Role of insulin and IGF-I in activation of muscle protein synthesis after oral feeding

Abstract

The aim was to evaluate the role of insulin and insulin-like growth factor I (IGF-I) in activation of muscle protein synthesis after oral feeding. Synthesis rate of globular and myofibrillar proteins in muscle tissue was quantified by a flooding dose of radioactive phenylalanine. Muscle tissue expression of IGF-I mRNA was measured. Normal (C57 Bl) and diabetic mice (type I and type II) were subjected to an overnight fast (18 h) with subsequent refeeding procedures for 3 h with either oral chow intake or provision of insulin, IGF-I, glucose, and amino acids. Anti-insulin and anti-IGF-I were provided intraperitoneally before oral refeeding in some experiments. An overnight fast reduced synthesis of both globular (38 +/- 3%) and myofibrillar proteins (54 +/- 3%) in skeletal muscles, which was reversed by oral refeeding. Muscle protein synthesis, after starvation/ refeeding, was proportional and similar to changes in skeletal muscle IGF-I mRNA expression. Diabetic mice responded quantitatively similarly to starvation/refeeding in muscle protein synthesis compared with normal mice (C57 Bl). Both anti-insulin and anti-IGF-I attenuated significantly the stimulation of muscle protein synthesis in response to oral feeding, whereas exogenous provision of either insulin or IGF-I to overnight-starved and freely fed mice did not clearly stimulate protein synthesis in skeletal muscles. Our results support the suggestion that insulin and IGF-I either induce or facilitate the protein synthesis machinery in skeletal muscles rather than exerting a true stimulation of the biosynthetic process during feeding.

Amino Acid Sufficiency and mTOR Regulate p70 S6 Kinase and eIF-4E BP1 through a Common Effector Mechanism

“…Concomitantly, the association of 4E with 4E-BP1 increases with starvation and diminishes with refeeding whereas the association of 4E with 4G, as expected responds in the reciprocal manner (20). As regards the relative importance of insulin versus nutrients in the control of 4E-BP1 phosphorylation, it is notable that the changes in phosphorylation of 4E-BP in response to fasting and feeding remain intact in NOD and ob/ob mice (20), diabetic models who fail to show any change in insulin concentration in response to these dietary maneuvers (2).…”

“…At least three sets of independently regulated site-specific p70 phosphorylations have been identified; one is a set of Ser/Thr-Pro motifs clustered in a psuedosubstrate autoinhibitory domain in the noncatalytic carboxyl-terminal tail (Ser-434, -441, and -447; Thr-444 in p70␣1) 2 (45,48). A second site is Thr-412, 2 located in a unique hydrophobic segment; homologous sites of regulatory phosphorylation have been identified in PKCs and c-Akt/ PKB (45).…”

“…The contribution of the nutrients themselves to the regulation of protein synthesis as compared with the concomitant hormonal responses has been the object of considerable study. Insulin, e.g., is well known to stimulate protein synthesis in skeletal muscle; however, much evidence indicates that a major portion of the increase in the skeletal muscle protein synthesis in vivo seen on refeeding is independent of changes in insulin and perhaps attributable to the nutrients themselves (2). Nevertheless, in vivo it is difficult to isolate the contributions of amino acids and other nutrients from those of insulin, insulin-like growth factors, and other regulators whose availability in vivo is altered by nutrients.…”

Nutritional Interventions as Potential Strategy to Minimize Exercise-Induced Muscle Injuries in Sports

“…It has been shown that hyperaminoacidemia stimulates amino acid transport and net MPS, unlike carbohydrate administration both in the young [173] and in the elderly [174]. The effects on protein synthesis arise independently of changes in anabolic hormone concentration [175,176], although insulin is required for the effects of EAA on translation [177]. Among EAA, Branched chain amino acids (BCAA: leucine, isoleucine and valine) play a very important role as nutrient signals that regulates MPS through the stimulation of insulin-independent and rapamycin-sensitive pathways [178,179].…”

Time Course of Leucine-induced 4E-BP1 and S6K1 Phosphorylation in the Liver and Skeletal Muscle of Rats.

“…Feeding induces a rapid increase in the synthesis rate of total proteins in the skeletal muscle (1)(2)(3)(4) and liver (1,4) of growing postabsorptive animals. The signals responsible for stimulating protein synthesis remain unclear, though several studies have suggested a media tory role for amino acids in this anabolic response (4)(5)(6)(7)(8).…”