AUTHOR=Benatti Fabiana B. , Miyake Cíntia N. H. , Dantas Wagner S. , Zambelli Vanessa O. , Shinjo Samuel K. , Pereira Rosa M. R. , Silva Maria Elizabeth R. , Sá-Pinto Ana Lúcia , Borba Eduardo , Bonfá Eloisa , Gualano Bruno 

TITLE=Exercise Increases Insulin Sensitivity and Skeletal Muscle AMPK Expression in Systemic Lupus Erythematosus: A Randomized Controlled Trial

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00906

DOI=10.3389/fimmu.2018.00906

ISSN=1664-3224

ABSTRACT=Systemic lupus erythematosus (SLE) patients may show increased insulin resistance (IR) when compared with their healthy peers. Exercise training has been shown to improve insulin sensitivity in other insulin-resistant populations, but it has never been tested in SLE. Therefore, the aim of the present study was to assess the efficacy of a moderate-intensity exercise training program on insulin sensitivity and potential underlying mechanisms in SLE patients with mild/inactive disease. A 12-wk, randomized-controlled trial was conducted. Nineteen SLE patients were randomly assigned into two groups: trained (SLE-TR, n=9) and non-trained (SLE-NT, n=10). Before and after 12 weeks of the exercise training program, patients underwent a meal test (MT), from which surrogates of insulin sensitivity and beta-cell function were determined. Muscle biopsies were performed after the MT for the assessment of total and membrane GLUT4 and proteins related to insulin signaling (Akt and AMPK). SLE-TR showed, when compared with SLE-NT, significant decreases in fasting insulin (-39% vs. +14%, p=0.009, effect size [ES]=-1.0) and in the insulin response to MT (-23% vs. +21%, p=0.007, ES=-1.1), HOMA-IR (-30% vs. +15%, p=0.005, ES=-1.1), a tendency towards decreased proinsulin response to MT (-19% vs. +6%, p=0.07, ES=-0.-9) and increased glucagon response to MT (+3% vs. -3%, p=0.09, ES=0.6), and significant increases in the Matsuda index (+66% vs. -31%, p=0.004, ES=0.9) and fasting glucagon (+4% vs. -8%, p=0.03, ES=0.7). No significant differences between SLT-TR and SLT-NT were observed in fasting glucose, glucose response to MT and insulinogenic index (all p>0.05). SLE-TR showed a significant increase in AMPK Thr 172 phosphorylation when compared to SLE-NT (+73% vs. -12%, p=0.014, ES=1.3), whereas no significant differences between groups were observed in Akt Ser 473 phosphorylation, total and membrane GLUT4 expression and GLUT4 translocation (all p>0.05). In conclusion, a 12-week moderate-intensity aerobic exercise training program improved insulin sensitivity in SLE patients with mild/inactive disease. This effect appears to be partially mediated by the increased insulin-stimulated skeletal muscle AMPK phosphorylation. Registered at clinicaltrial.gov as NCT01515163.