Melatonin inhibits tunicamycin-induced endoplasmic reticulum stress and insulin resistance in skeletal muscle cells.

The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide. Melatonin possesses various beneficial metabolic actions, decreased levels of which may accelerate T2D. Endoplasmic reticulum stress (ERS) has been linked to insulin resistance in multiple tissues, but the role of melatonin on ERS and insulin resistance in skeletal muscle has not yet been investigated. In this study, the results showed that tunicamycin decreased insulin-stimulated Akt phosphorylation, but promoted the phosphorylation of protein kinase R-like ER protein kinase (PERK) time-dependently in C2C12 cells. Consistently, ERS gene markers, including binding immunoglobulin protein (BIP)/glucose regulated protein 78 (GRP78) expression and the splicing of X box binding protein 1 (XBP-1), were activated by tunicamycin time-dependently. Interestingly, melatonin pretreatment reversed the elevated PERK phosphorylation, as well as the activation of Bip expression and XBP-1 splicing, and prevented the inhibitory effect of tunicamycin on Akt phosphorylation. In addition, the insulin-provoked glucose transport was reduced by tunicamycin, and then promoted by melatonin pretreatment. A strong phosphorylation of inositol-requiring enzyme 1 (IRE-1), c-JUN NH2-terminal kinase (JNK), and insulin receptor substrate 1 (IRS-1) serine, and simultaneously, a dramatic decrease of IRS-1 tyrosine phosphorylation were observed in the presence of tunicamycin, leading to a blockade of insulin signaling, which was reversed by melatonin pretreatment. Furthermore, luzindole pretreatment acted inversely with melatonin action on glucose uptake and insulin signaling. Therefore, these results demonstrated that melatonin pretreatment inhibited the activated role of tunicamycin on ERS and insulin resistance through melatonin receptor-mediated IRE-1/JNK/IRS-1 insulin signaling in skeletal muscle cells.

Kawasaki Disease- Management Strategies Given Symptoms Overlap to COVID-19: A Review.

Kawasaki disease is an acute, self-limiting vasculitis in children. Early treatment is necessary to prevent cardiovascular complications. The acute phase of Kawasaki disease may present with hemodynamic instability. An association between viral respiratory infections and Kawasaki disease has been reported. Studies have shown that Kawasaki and Kawasaki-like disease may be associated with and have symptoms overlapping COVID-19. Children with COVID-19 may present as Kawasaki-like disease with pediatric inflammatory multisystem syndrome, or macrophage activation syndrome. Clinicians need to be aware of the early diagnosis and management of Kawasaki disease to prevent the development of coronary artery aneurysms. The symptoms overlap of multisystem inflammatory disease seen in COVID-19 adds to the difficulties in timely diagnosis and treatment. Children with Kawasaki disease require regular follow-up plans for coronary artery aneurysms. This adds to the difficulties during the changed environment of COVID-19 for control and prevention. Missed diagnosis and early treatment of Kawasaki disease with immunoglobulin and aspirin results in the development of coronary artery aneurysm in up to 25% of cases, with grave consequences. Here, we briefly review the management of typical and atypical Kawasaki disease which has symptoms overlapping with the multisystem inflammatory disease as seen in COVID-19.