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RORB and RORC associate with human islet dysfunction and inhibit insulin secretion in INS-1 cells

Taneera, Jalal LU ; Mohammed, Abdul Khader; Dhaiban, Sarah; Hamad, Mawieh; Prasad, Rashmi B. LU ; Sulaiman, Nabil and Salehi, Albert LU (2019) In Islets 11(1). p.10-20
Abstract


Little is known about the expression and function of Retinoic acid-related orphan receptors (RORA, B, and C) in pancreatic β cells. Here in, we utilized cDNA microarray and RNA sequencing approaches to investigate the expression pattern of ROR receptors in normal and diabetic human pancreatic islets. Possible correlations between RORs expression and HbA
1c
levels as well as insulin secretory capacity in isolated human islets were evaluated. The impact of RORB and RORC expression on insulin secretion in INS-1 (832/13) cells was validated as... (More)


Little is known about the expression and function of Retinoic acid-related orphan receptors (RORA, B, and C) in pancreatic β cells. Here in, we utilized cDNA microarray and RNA sequencing approaches to investigate the expression pattern of ROR receptors in normal and diabetic human pancreatic islets. Possible correlations between RORs expression and HbA
1c
levels as well as insulin secretory capacity in isolated human islets were evaluated. The impact of RORB and RORC expression on insulin secretion in INS-1 (832/13) cells was validated as well. While RORA was the highest expressed gene among the three RORs in human islet cells, RORC was the highest expressed in INS-1 cells (832/13) and while RORB was the lowest expressed gene in human islet cells, RORA was the highest expressed in INS-1 cells (832/13). The expression of RORB and RORC was significantly lower in diabetic/hyperglycemic donors as compared with non-diabetic counterparts. Furthermore, while the expression of RORB correlated positively with insulin secretion and negatively with HbA
1c
, that of RORC correlated negatively with HbA
1c
. The expression pattern of RORA did not correlate with either of the two parameters. siRNA silencing of RORB or RORC in INS-1 (832/13) cells resulted in a significant downregulation of insulin mRNA expression and insulin secretion. These findings suggest that RORB and RORC are part of the molecular cascade that regulates insulin secretion in pancreatic β cells; and insight that provides for further work on the potential therapeutic utility of RORB and RORC genes in β cell dysfunction in type 2 diabetes.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diabetes, gene expression microarray, human islets, INS-1 (832/13), insulin secretion, Retinoic acid-related orphan receptor
in
Islets
volume
11
issue
1
pages
11 pages
publisher
Landes Bioscience
external identifiers
  • scopus:85061809116
ISSN
1938-2014
DOI
10.1080/19382014.2019.1566684
language
English
LU publication?
yes
id
b21271b1-160c-46b7-9f19-72a3292e2d37
date added to LUP
2019-03-04 08:53:51
date last changed
2019-03-27 04:39:36
@article{b21271b1-160c-46b7-9f19-72a3292e2d37,
  abstract     = {<p><br>
                                                         Little is known about the expression and function of Retinoic acid-related orphan receptors (RORA, B, and C) in pancreatic β cells. Here in, we utilized cDNA microarray and RNA sequencing approaches to investigate the expression pattern of ROR receptors in normal and diabetic human pancreatic islets. Possible correlations between RORs expression and HbA                             <br>
                            <sub>1c</sub><br>
                                                          levels as well as insulin secretory capacity in isolated human islets were evaluated. The impact of RORB and RORC expression on insulin secretion in INS-1 (832/13) cells was validated as well. While RORA was the highest expressed gene among the three RORs in human islet cells, RORC was the highest expressed in INS-1 cells (832/13) and while RORB was the lowest expressed gene in human islet cells, RORA was the highest expressed in INS-1 cells (832/13). The expression of RORB and RORC was significantly lower in diabetic/hyperglycemic donors as compared with non-diabetic counterparts. Furthermore, while the expression of RORB correlated positively with insulin secretion and negatively with HbA                             <br>
                            <sub>1c</sub><br>
                                                         , that of RORC correlated negatively with HbA                             <br>
                            <sub>1c</sub><br>
                                                         . The expression pattern of RORA did not correlate with either of the two parameters. siRNA silencing of RORB or RORC in INS-1 (832/13) cells resulted in a significant downregulation of insulin mRNA expression and insulin secretion. These findings suggest that RORB and RORC are part of the molecular cascade that regulates insulin secretion in pancreatic β cells; and insight that provides for further work on the potential therapeutic utility of RORB and RORC genes in β cell dysfunction in type 2 diabetes.                         <br>
                        </p>},
  author       = {Taneera, Jalal and Mohammed, Abdul Khader and Dhaiban, Sarah and Hamad, Mawieh and Prasad, Rashmi B. and Sulaiman, Nabil and Salehi, Albert},
  issn         = {1938-2014},
  keyword      = {Diabetes,gene expression microarray,human islets,INS-1 (832/13),insulin secretion,Retinoic acid-related orphan receptor},
  language     = {eng},
  number       = {1},
  pages        = {10--20},
  publisher    = {Landes Bioscience},
  series       = {Islets},
  title        = {RORB and RORC associate with human islet dysfunction and inhibit insulin secretion in INS-1 cells},
  url          = {http://dx.doi.org/10.1080/19382014.2019.1566684},
  volume       = {11},
  year         = {2019},
}