Skeletal muscle mitochondrial protein metabolism and... : Current Opinion in Clinical Nutrition & Metabolic Care (original) (raw)

Protein and amino acid metabolism

Skeletal muscle mitochondrial protein metabolism and function in ageing and type 2 diabetes

Department of Clinical Morphological and Technological Sciences, Institute of Clinical Medicine, University of Trieste, Trieste, Italy

Correspondence to Rocco Barazzoni, Clinica Medica, Ospedale Cattinara, Strada di Fiume 447, Trieste, Italy Tel: +39 040 3994416; fax: +39 040 3994593; e-mail: [email protected]

Abbreviations

ATP: adenosine triphosphate

FSR: fractional synthesis rate

UCP: uncoupling protein

Abstract

Purpose of review

Mitochondria are the site of oxidative substrate utilization to produce adenosine triphosphate for normal tissue function. Tissue substrate utilization is impaired in ageing and type 2 diabetes. Defects in mitochondrial gene expression, protein synthesis and function occur with ageing in various tissues including skeletal muscle, and are emerging in individuals with type 2 diabetes. The current review will discuss advances in the understanding of skeletal muscle mitochondrial alterations associated with age and type 2 diabetes.

Recent findings

Insulin acutely stimulates skeletal muscle mitochondrial protein synthesis and adenosine triphosphate production. These insulin effects are impaired in insulin-resistant patients with type 2 diabetes who also exhibit defective basal muscle mitochondrial function. The age-related reduction in mitochondrial adenosine triphosphate production has been confirmed in vivo in skeletal muscle in humans and rodents.

Summary

The emerging concept that insulin stimulates mitochondrial protein synthesis and function indicates potential novel molecular mechanisms of metabolic defects in type 2 diabetes, particularly in the post-prandial period characterized by acute increments of plasma insulin concentrations. The potential relationship between insulin resistance and basal post-absorptive muscle mitochondrial defects should be further investigated. As ageing is characterized by insulin resistance, the hypothesis that impaired insulin action could contribute to age-related muscle mitochondrial dysfunction, and metabolic alterations should be addressed.