Defect of insulin signal in peripheral tissues: important role of ceramide

In healthy people,balance between glucose production and its utilization is precisely controlled.When circulating glucose reaches a critical threshold level,pancreaticβcells secrete insulin that has two major actions:to lower circulating glucose levels by facilitating its uptake mainly into skeletal muscle while inhibiting its production by the liver.Interestingly,dietary triglycerides are the main source of fatty acids to fulfill energy needs of oxidative tissues.Normally,the unconsumed fraction of excess of fatty acids is stored in lipid droplets that are localized in adipocytes to provide energy during fasting periods.Thus,adipose tissue acts as a trap for fatty acid excess liberated from plasma triglycerides.When the buffering action of adipose tissue to store fatty acids is impaired,fatty acids that build up in othertissues are metabolized as sphingolipid derivatives such as ceramides.Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway.

Interactions between diabetes and COVID-19:A narrative review

Diabetes,whether due to pancreatic beta cells insufficiency or peripheral resistance to insulin,has been suggested as a risk factor of developing severe acute respiratory disease coronavirus-2(SARS-CoV-2)infections.Indeed,diabetes has been associated with a higher risk of infections and higher risk of developing severe forms of coronavirus disease 2019(COVID-19)related pneumonia.Diabetic patients often present associated comorbidities such as obesity,hypertension and cardiovascular diseases,and complications of diabetes,including chronic kidney disease,vasculopathy and relative immune dysfunction,all of which make them more susceptible to infectious complications.Moreover,they often present lowgrade inflammation with increased circulating interleukin levels,endothelial susceptibility to inflammation and dysfunction,and finally,hyperglycemia,which increases this risk.Additionally,corticosteroids,which count among the few medications which showed benefit on survival and mechanical ventilation requirement in COVID-19 pneumonia in large randomized controlled trials,are associated to new onsets of diabetes,and metabolic disorders in patients with previous history of diabetes.Finally,SARS-CoV-2 via the alternate effects of the renin-angiotensin system,mediated by the angiotensin-converting-enzyme 2,was also associated with insulin resistance in key tissues involved in glucose homeostasis,such as liver,skeletal muscles,and adipose tissue;and also,with impaired insulin secretion by pancreaticβ-cells.In this work,we reviewed all elements which may help understand how diabetes affects patients with COVID-19,how treatments affect outcomes in patients with COVID-19,how they may cause new onsets of diabetes,and finally review how SARS-CoV-2 may inherently be a risk factor of developing diabetes,through immune-mediated diabetogenic mechanisms.