Abstract

Humanin (HN) is a mitochondrially encoded and secreted peptide linked to glucose metabolism and tissue protecting mechanisms. Whether skeletal muscle HN gene or protein expression is influenced by exercise remains unknown. In this intervention study we show, for the first time, that HN protein levels increase in human skeletal muscle following 12 weeks of resistance training in persons with prediabetes. Male subjects (n = 55) with impaired glucose regulation (IGR) were recruited and randomly assigned to resistance training, Nordic walking or a control group. The exercise interventions were performed three times per week for 12 weeks with progressively increased intensity during the intervention period. Biopsies from the vastus lateralis muscle and venous blood samples were taken before and after the intervention. Skeletal muscle and serum protein levels of HN were analyzed as well as skeletal muscle gene expression of the mitochondrially encoded gene MT‐RNR2, containing the open reading frame for HN. To elucidate mitochondrial training adaptation, mtDNA, and nuclear DNA as well as Citrate synthase were measured. Skeletal muscle HN protein levels increased by 35% after 12 weeks of resistance training. No change in humanin protein levels was seen in serum in any of the intervention groups. There was a significant correlation between humanin levels in serum and the improvements in the 2 h glucose loading test in the resistance training group. The increase in HN protein levels in skeletal muscle after regular resistance training in prediabetic males may suggest a role for HN in the regulation of glucose metabolism. Given the preventative effect of exercise on diabetes type 2, the role of HN as a mitochondrially derived peptide and an exercise‐responsive mitokine warrants further investigation.

Highlights

  • Regular exercise leads to adaptations such as mitochondrial biogenesis, improved oxidative capacity, and hypertrophy of skeletal muscle (Holloszy and Booth 1976).Aerobic and anaerobic training have been recognized to improve glucose control in conditions such as impaired glucose tolerance and type 2 diabetes (Kelley et al 2002; Earnest 2008)

  • Differences in HN baseline values were seen between the groups, with higher values in the Nordic walking (NW) and C group compared to the resistance training (RT) group (P < 0.05) and were accounted for as a covariate in the statistical analysis

  • Humanin was analyzed in serum but there was no significant change over time or between the groups (Fig. 1B)

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Summary

Introduction

Regular exercise leads to adaptations such as mitochondrial biogenesis, improved oxidative capacity, and hypertrophy of skeletal muscle (Holloszy and Booth 1976). Aerobic and anaerobic training have been recognized to improve glucose control in conditions such as impaired glucose tolerance and type 2 diabetes (Kelley et al 2002; Earnest 2008). Factors and molecules produced in skeletal muscle and secreted a 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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