title: 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. 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.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden eva-karin.gidlund@ki.se.
authors.forename: Eva-Karin
authors.initials: EK
authors.lastname: Gidlund
authors.affiliation: Neuropediatrics Unit, Department of Women's and Children's Health, Karolinska Institutet and Astrid Lindgren's Pediatric Hospital, Stockholm, Sweden.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: von Walden
authors.affiliation: Institute of Biomedicine, Sports and exercise medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Venojärvi
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Risérus
authors.affiliation: Paavo Nurmi Centre and Departmen of Health & Physical Activity, University of Turku, Turku, Finland.
authors.forename: Olli J
authors.initials: OJ
authors.lastname: Heinonen
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Norrbom
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl Johan
authors.initials: CJ
authors.lastname: Sundberg
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D011236:Prediabetic State / Q000097:blood / Q000378:metabolism*; D055070:Resistance Training
chemical_list: D001786:Blood Glucose; D047908:Intracellular Signaling Peptides and Proteins; C427211:humanin; D002950:Citrate (si)-Synthase
keywords: Exercise; human; humanin; impaired glucose regulation; skeletal muscle