Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic Donors

Abstract

Cellular entry of SARS-CoV-2 is thought to occur through the binding of viral spike S1 protein to <i>ACE2</i>. The entry process involves priming of the S protein by <i>TMPRSS2</i> and <i>ADAM17</i>, which collectively mediate the binding and promote ACE2 shedding. In this study, microarray and RNA-sequencing (RNA-seq) expression data were utilized to profile the expression pattern of <i>ACE2</i>, <i>ADAM17</i>, and <i>TMPRSS2</i> in type 2 diabetic (T2D) and non-diabetic human pancreatic islets. Our data show that pancreatic islets express all three receptors irrespective of diabetes status. The expression of <i>ACE2</i> was significantly increased in diabetic/hyperglycemic islets compared to non-diabetic/normoglycemic. Islets from female donors showed higher <i>ACE2</i> expression compared to males; the expression of <i>ADAM17</i> and <i>TMPRSS2</i> was not affected by gender. The expression of the three receptors was statistically similar in young (≤40 years old) versus old (≥60 years old) donors. Obese (BMI > 30) donors have significantly higher expression levels of <i>ADAM17</i> and <i>TMPRSS2</i> relative to those from non-obese donors (BMI < 25). <i>TMPRSS2</i> expression correlated positively with HbA1c and negatively with age, while <i>ADAM17</i> and <i>TMPRSS2</i> correlated positively with BMI. The expression of the three receptors was statistically similar in muscle and subcutaneous adipose tissues obtained from diabetic and nondiabetic donors. Lastly, <i>ACE2</i> expression was higher in sorted pancreatic β-cell relative to other endocrine cells. In conclusion, <i>ACE2</i> expression is increased in diabetic human islets. More studies are required to investigate whether variations of <i>ACE2</i> expression could explain the severity of COVID-19 infection-related symptoms between diabetics and non-diabetic patients.