Humanin skeletal muscle protein levels increase after resistance training in men with impaired glucose metabolism

Abstract

Humanin (HN) is a mitochondrially encoded and secreted peptide linked to glucose metabolism and tissue protecting mechanisms. Plasma HN levels are lower in people with type 2 diabetes. Whether skeletal muscle HN expression is influenced by exercise is unknown. Therefore, the aim of this study was to investigate serum and skeletal muscle HN levels in men with impaired glucose control in response to 12 weeks of either resistance or aerobic (nordic walking) training.Men (n=55) with impaired glucose regulation (IGR) were recruited and randomly assigned to resistance training (RT), Nordic walking (NW) or control (CON). Subjects trained three times per week for twelve 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. A 2‐hr oral glucose tolerance test (OGTT) with 75 g of glucose loading was performed before and after the intervention period. Skeletal muscle and serum HN protein levels and skeletal muscle gene expression of MT‐NRN2 (the 16S gene), MT‐NRN1 (the 12S gene) and HNM1 were analyzed.Skeletal muscle HN protein levels increased by 35 % after twelve weeks of resistance training (time × group interaction p=0.022). No significant interactions over time were seen in the NW or the C groups (ns). In the RT group, ΔHN serum protein concentration was correlated to the improvement of 2‐hr glucose loading test (R= 0.597, p=0.019). Twelve weeks of either RT or NW did not change mRNA levels of MT‐NRN2, MT‐NRN1 or of HNM1. There was a significant increase in citrate synthase activity in the RT group (1.8‐fold ± 0.47 p<0.05, time × group interaction p=0.027).HN protein levels in skeletal muscle increase after regular resistance training in pre‐diabetic men. The significant correlation between ΔHN serum levels and improvements in the 2‐hr time point of the OGTT suggests 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.Support or Funding InformationThe study was supported by grants from the Research Council for Physical Education and Sports, of the Finnish Ministry of Education, of Turku University of Applied Sciences R&D program and from Karolinska Institutet, Department of Physiology & Pharmacology.