Abstract
BACKGROUND: There is evidence demonstrating the risk of developing diabetes mellitus because of SARS-CoV-2 infection. Therefore, further research is needed to determine pathological mechanisms at which SARS-CoV-2 induces diabetes mellitus. This study therefore aims to understand the effect of SARS-CoV-2 Main protease (M(pro)) on glucose uptake and GLUT-4 translocation as well as AKT, GLUT-4, and IL-6 expression in skeletal muscle (C2C12). METHODS: In this study, C2C12 cell preparations were exposed to different concentrations of M(pro) (2.5, 5, 10, 20, 40, 80, and 160 nmol/mL) for 24 h to evaluate cytotoxicity and glucose uptake. For further assays, only the higher concentrations (40, 80, and 160 nmol/mL) were used. The impact of M(pro) on cell viability, glucose uptake, AKT, GLUT-4 and IL-6 expression, GLUT-4 translocation as well as lipid peroxidation were analyzed. RESULTS: Following 24 h of treatment with SARS-CoV-2 M(pro), C2C12 cells were viable. The baseline and insulin-stimulated glucose uptake were impaired in the C2C12 cell line. M(pro) also compromised GLUT4 translocation and expression in the C2C12 cell line compared to the control. Baseline and Insulin-stimulated AKT were not significantly altered in the presence of M(pro). Intracellular and extracellular IL-6 levels were also affected by M(pro). An increase in MDA levels, a marker for lipid peroxidation, was observed. CONCLUSIONS: The observations suggest that the SARS-CoV-2 M(pro) may be inducing an insulin-resistant state and dysregulation of glucose metabolism. Further studies are warranted to fully elucidate the mechanisms underlying the development of new-onset diabetes mellitus in patients with a history of COVID-19.