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

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 215 ◽  
Author(s):  
Jalal Taneera ◽  
Waseem El-Huneidi ◽  
Mawieh Hamad ◽  
Abdul Khader Mohammed ◽  
Esraa Elaraby ◽  
...  

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.

2016 ◽  
Vol 229 (2) ◽  
pp. 123-132 ◽  
Author(s):  
Charlotte Barbieux ◽  
Géraldine Parnaud ◽  
Vanessa Lavallard ◽  
Estelle Brioudes ◽  
Jérémy Meyer ◽  
...  

The aim of this study was to evaluate the location of PP and δ cells in relation to the vascularization within human pancreatic islets. To this end, pancreas sections were analysed by immunofluorescence using antibodies against endocrine islet and endothelial cells. Staining in different islet areas corresponding to islet cells adjacent or not to peripheral or central vascular channels was quantified by computerized morphometry. As results, α, PP and δ cells were preferentially found adjacent to vessels. In contrast to α cells, which were evenly distributed between islet periphery and intraislet vascular channels, PP and δ cells had asymmetric and opposite distributions: PP staining was higher and somatostatin staining was lower in the islet periphery than in the area around intraislet vascular channels. Additionally, frequencies of PP and δ cells were negatively correlated in the islets. No difference was observed between islets from the head and the tail of the pancreas, and from type 2 diabetic and non-diabetic donors. In conclusion, the distribution of δ cells differs from that of PP cells in human islets, suggesting that vessels at the periphery and at the centre of islets drain different hormonal cocktails.


2003 ◽  
Vol 284 (2) ◽  
pp. E443-E448 ◽  
Author(s):  
A. S. Lihn ◽  
T. Østergård ◽  
B. Nyholm ◽  
S. B. Pedersen ◽  
B. Richelsen ◽  
...  

Adiponectin is suggested to be an important mediator of insulin resistance. Therefore, we investigated the association between adiponectin and insulin sensitivity in 22 healthy first-degree relatives (FDR) to type 2 diabetic patients and 13 matched control subjects. Subcutaneous adipose tissue biopsies were taken before and after a hyperinsulinemic euglycemic clamp. FDR subjects were insulin resistant, as indicated by a reduced Mvalue (4.44 vs. 6.09 mg · kg−1· min−1, P < 0.05). Adiponectin mRNA expression was 45% lower in adipose tissue from FDR compared with controls ( P < 0.01), whereas serum adiponectin was similar in the two groups (6.4 vs. 6.6 μg/ml, not significant). Insulin infusion reduced circulating levels of adiponectin moderately (11–13%) but significantly in both groups ( P < 0.05). In the control group, adiponectin mRNA levels were negatively correlated with fasting insulin ( P < 0.05) and positively correlated with insulin sensitivity ( P < 0.05). In contrast, these associations were not found in the FDR group. In conclusion, FDR have reduced adiponectin mRNA in subcutaneous adipose tissue but normal levels of circulating adiponectin. Adiponectin mRNA levels are positively correlated with insulin sensitivity in control subjects but not in FDR. These findings indicate dysregulation of adiponectin gene expression in FDR.


2012 ◽  
Vol 31 (6) ◽  
pp. 1405-1426 ◽  
Author(s):  
Michael Volkmar ◽  
Sarah Dedeurwaerder ◽  
Daniel A Cunha ◽  
Matladi N Ndlovu ◽  
Matthieu Defrance ◽  
...  

Islets ◽  
2009 ◽  
Vol 1 (2) ◽  
pp. 102-105 ◽  
Author(s):  
Suhail Al-Salam ◽  
Raheed Hameed ◽  
Hasan Parvez ◽  
Ernest Adeghate

2000 ◽  
Vol 1 (2) ◽  
pp. 81-88 ◽  
Author(s):  
Michael A. Statnick ◽  
Lisa S. Beavers ◽  
Laura J. Conner ◽  
Helena Corominola ◽  
Dwayne Johnson ◽  
...  

We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFα and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes.


2014 ◽  
Vol 52 (3) ◽  
pp. 523-530 ◽  
Author(s):  
Guido Sebastiani ◽  
Agnese Po ◽  
Evelina Miele ◽  
Giuliana Ventriglia ◽  
Elena Ceccarelli ◽  
...  

2019 ◽  
Author(s):  
Sergiy V. Korol ◽  
Zhe Jin ◽  
Bryndis Birnir

AbstractIn pancreatic islets the major cell-types are α, β and δ cells, secreting the hormones glucagon (GCG), insulin (INS) and somatostatin (SST), respectively. The GABA (γ-aminobutyric acid) signalling system is expressed in human pancreatic islets. We have previously used single-cell RT-PCR in combination with current recordings to correlate expression of single hormone transcript with functional GABAA receptor (iGABAAR) properties in islets. Here we extended these studies to islet cells from non-diabetic and type 2 diabetic donors that express mRNAs for more than one hormone. We detected cells expressing double (α/β, α/δ, β/δ cell-types) and triple (α/β/δ cell-type) hormone transcripts. The most common mixed-identity cell-type was the α/β group where the cells could be grouped into β- and α-like subgroups. The β-like cells had low GCG/INS expression ratio (< 0.6) and significantly higher frequency of single-channel iGABAAR openings than the α-like cells where the GCG/INS expression ratio was high (> 1.2). The difference in expression levels and single channel iGABAAR characteristics varied in the α/β/δ cell-type. No correlation was observed between the cell-types identity with time in culture or cell size. Clearly, multiple hormone transcripts can be expressed in islet cells whereas iGABAAR functional properties appear α or β cell specific.


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