Clinical Trial Registration

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=9 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-week, 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 AMP-activated protein kinase (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), homeostasis model assessment IR (−30 vs. +15%, p = 0.005, ES = −1.1), a tendency toward 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.