ACE2 function in the pancreatic islet: Implications for relationship between SARS-CoV-2 and diabetes.

ABSTRACT

The molecular link between SARS-CoV-2 infection and susceptibility is not well understood. Nonetheless, a bi-directional relationship between SARS-CoV-2 and diabetes has been proposed. The angiotensin-converting enzyme 2 (ACE2) is considered as the primary protein facilitating SARS-CoV and SARS-CoV-2 attachment and entry into the host cells. Studies suggested that ACE2 is expressed in the endocrine cells of the pancreas including beta cells, in addition to the lungs and other organs; however, its expression in the islets, particularly beta cells, has been met with some contradiction. Importantly, ACE2 plays a crucial role in glucose homoeostasis and insulin secretion by regulating beta cell physiology. Given the ability of SARS-CoV-2 to infect human pluripotent stem cell-derived pancreatic cells in vitro and the presence of SARS-CoV-2 in pancreatic samples from COVID-19 patients strongly hints that SARS-CoV-2 can invade the pancreas and directly cause pancreatic injury and diabetes. However, more studies are required to dissect the underpinning molecular mechanisms triggered in SARS-CoV-2-infected islets that lead to aggravation of diabetes. Regardless, it is important to understand the function of ACE2 in the pancreatic islets to design relevant therapeutic interventions in combatting the effects of SARS-CoV-2 on diabetes pathophysiology. Herein, we detail the function of ACE2 in pancreatic beta cells crucial for regulating insulin sensitivity, secretion, and glucose metabolism. Also, we discuss the potential role played by ACE2 in aiding SARS-COV-2 entry into the pancreas and the possibility of ACE2 cooperation with alternative entry factors as well as how that may be linked to diabetes pathogenesis.