Insulin and amino acids both strongly participate to the... : Current Opinion in Clinical Nutrition & Metabolic Care (original) (raw)

Protein and amino acid metabolism

Insulin and amino acids both strongly participate to the regulation of protein metabolism

Prod'homme, Magali; Rieu, Isabelle; Balage, Michele; Dardevet, Dominique; Grizard, Jean

Protein, Metabolism and Nutrition Unit, INRA, Theix, France

Correspondence to Jean Grizard, Protein, Metabolism and Nutrition Unit, INRA, 63122 Theix, France Tel: +33 473 62 42 03; fax: +33 473 62 47 55; e-mail: [email protected]

Abbreviations

AARE: amino acid response element

AS: asparagine synthetase

ATA2: amino acid transporter system A

C/EBP: CCAAT/enhancer binding protein

CHOP: C/EBP homologous protein

eIF: eukaryotic initiation factor

4E-BP1: 4E-binding protein 1

mTOR: mammalian target of rapamycin

PKB: protein kinase B

S6K1: S6 kinase 1

Abstract

Purpose of review

The application of tracer kinetic methods, combined with measurements of the activity of components of the cellular signaling pathways involved in protein synthesis and degradation, affords new insights into the regulation of skeletal muscle protein metabolism in vivo in humans. Feeding is associated with an increase in protein synthesis and a decrease in proteolysis. These changes are mediated by feeding-induced increases in plasma concentrations of both nutrients and hormones.

Recent findings

Recent studies definitely demonstrated that insulin and amino acids directly interacted in promoting postprandial anabolism. However, the contribution of amino acids was abolished in old individuals in whom only insulin action persisted. There was a line of evidence that the effect of amino acids originates from leucine, which should not be viewed simply as a building block for protein synthesis, but as a signal in the regulation of cell functions. Although their cellular signaling pathways do not completely overlap, insulin and amino acids both activate the translation initiation of protein synthesis. Insulin presumably inhibits skeletal muscle protein degradation through a decrease in the activity of the ubiquitin proteasome-dependent pathway.

Summary

Whether or not amino acids modify insulin action and have specific effects on proteolysis has not yet been documented. At the molecular level, amino acids such as insulin modulate gene expression. Such studies are needed to gain a better understanding of the interactions between insulin and amino acids in the regulation of skeletal muscle protein anabolism.