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 ACE2. The entry process involves priming of the S protein by TMPRSS2 and ADAM17, 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 ACE2, ADAM17, and TMPRSS2 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 ACE2 was significantly increased in diabetic/hyperglycemic islets compared to non-diabetic/normoglycemic. Islets from female donors showed higher ACE2 expression compared to males; the expression of ADAM17 and TMPRSS2 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 ADAM17 and TMPRSS2 relative to those from non-obese donors (BMI < 25). TMPRSS2 expression correlated positively with HbA1c and negatively with age, while ADAM17 and TMPRSS2 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, ACE2 expression was higher in sorted pancreatic β-cell relative to other endocrine cells. In conclusion, ACE2 expression is increased in diabetic human islets. More studies are required to investigate whether variations of ACE2 expression could explain the severity of COVID-19 infection-related symptoms between diabetics and non-diabetic patients.

Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19

“…Obesity is associated with an increased risk of COVID-19-associated morbidity and mortality ( Hussain et al., 2020 ; Nakeshbandi et al., 2020 ; Tartof et al., 2020 ). Taneera et al. (2020) observed no relationship between ACE2 and BMI in isolated pancreatic islets analyzed by microarray.…”

SARS-CoV-2 Receptor Angiotensin I-Converting Enzyme Type 2 (ACE2) Is Expressed in Human Pancreatic β-Cells and in the Human Pancreas Microvasculature

“…Of note, such datasets rely on bor a-cells bulk RNA-seq and do not suffer from common limitations present in single-cell RNA-seq (49), which usually detects only 1,000-3,000 genes/cell, thus representing a minor fraction (25-30%) of the total number of genes identified by bulk cells RNA sequencing (>20,000 genes). Another recent study analyzed SARS-CoV-2 host receptors expression using two different methods (microarray and bulk RNA-seq) and further confirmed that ACE2 is indeed expressed in human pancreatic islets and also demonstrated that ACE2 expression was higher in sorted pancreatic b-cells relative to other endocrine cells (66). Additional evidence of ACE2 expression in endocrine pancreas and in b-cells derive also from mouse studies, which demonstrated ACE2 expression in insulin-producing cells as well as its critical role in the regulation of b-cell phenotype and function (67)(68)(69)(70).…”

SARS-CoV-2 receptor Angiotensin I-Converting Enzyme type 2 (ACE2) is expressed in human pancreatic β-cells and in the human pancreas microvasculature

“…Of note, such datasets rely on β- or α-cells bulk RNA-seq and do not suffer from common limitations present in single-cell RNA seq (65), which usually detects only 1,000-3,000 genes/cell, thus representing a minor fraction (25-30%) of the total number of genes identified by bulk cells RNA sequencing (>20,000 genes). Another recent study analyzed SARS-CoV-2 host receptors expression using two different methods (microarray and bulk RNA-seq) and further confirmed that ACE2 is indeed expressed in human pancreatic islets, and also demonstrated that ACE2 expression was higher in sorted pancreatic β-cells relative to other endocrine cells (66). Additional evidence of ACE2 expression in endocrine pancreas and in β-cells derive also from mouse studies, which demonstrated ACE2 expression in insulin-producing cells as well as its critical role in the regulation of β-cell phenotype and function (67–70).…”