Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells

The COVID-19 pandemic has revealed a bidirectional relationship between SARS-CoV-2 infection and diabetes mellitus. Existing evidence strongly suggests hyperglycemia as an independent risk factor for severe COVID-19, resulting in increased morbidity and mortality. Conversely, recent studies have reported new-onset diabetes following SARS-CoV-2 infection, hinting at a potential direct viral attack on pancreatic beta cells. In this review, we explore how hyperglycemia, a hallmark of diabetes, might influence SARS-CoV-2 entry and accessory proteins in pancreatic β-cells. We examine how the virus may enter and manipulate such cells, focusing on the role of the spike protein and its interaction with host receptors. Additionally, we analyze potential effects on endosomal processing and accessory proteins involved in viral infection. Our analysis suggests a complex interplay between hyperglycemia and SARS-CoV-2 in pancreatic β-cells. Understanding these mechanisms may help unlock urgent therapeutic strategies to mitigate the detrimental effects of COVID-19 in diabetic patients and unveil if the virus itself can trigger diabetes onset.