Sirtuin 1 is not required for contraction-stimulated glucose uptake in mouse skeletal muscle

• Published in: Journal of applied physiology (1985) Vol. 130; no. 6; pp. 1893 - 1902
• Main Authors: Kang, Ji Hyun, Park, Ji E, Dagoon, Jason, Masson, Stewart W C, Merry, Troy L, Bremner, Shannon N, Dent, Jessica R, Schenk, Simon
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.06.2021
• Subjects: Adaptation; Contraction; Deoxyglucose; Genotypes; Glucose; Males; Muscle contraction; Muscles; Musculoskeletal system; NAD; Perturbation; Sex; SIRT1 protein; Skeletal muscle; exercise; sex dimorphism; deacetylase; 2-deoxyglucose
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00065.2021

While it has long been known that contraction robustly stimulates skeletal muscle glucose uptake, the molecular steps regulating this increase remain incompletely defined. The mammalian ortholog of Sir2, sirtuin 1 (SIRT1), is an NAD -dependent protein deacetylase that is thought to link perturbations in energy flux associated with exercise to subsequent cellular adaptations. Nevertheless, its role in contraction-stimulated glucose uptake has not been described. The objective of this study was to determine the importance of SIRT1 to contraction-stimulated glucose uptake in mouse skeletal muscle. Using a radioactive 2-deoxyglucose uptake (2DOGU) approach, we measured ex vivo glucose uptake in unstimulated (rested) and electrically-stimulated (100 Hz contraction every 15s for 10 min; contracted) extensor digitorum longus (EDL) and soleus from ~15 week old male and female mice with muscle-specific knockout of SIRT1 deacetylase activity (mKO) and their wildtype (WT) littermates. Skeletal muscle force decreased over the contraction protocol, although there were no differences in the rate of fatigue between genotypes. In EDL and soleus, depletion of SIRT1 deacetylase activity did not affect contraction-induced increase in glucose uptake in either sex. Interestingly, the absolute rate of contraction-stimulated 2DOGU was ~1.4-fold higher in female compared to male mice, regardless of muscle type. Taken together, our findings demonstrate that SIRT1 is not required for contraction-stimulated glucose uptake in mouse skeletal muscle. Moreover, to our knowledge, this is the first demonstration of sex-based differences in contraction-stimulated glucose uptake in mouse skeletal muscle.