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Rashmi Prasad

Rashmi Prasad

Assistant researcher

Rashmi Prasad

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

Author

  • Jalal Taneera
  • Abdul Khader Mohammed
  • Sarah Dhaiban
  • Mawieh Hamad
  • Rashmi B. Prasad
  • Nabil Sulaiman
  • Albert Salehi

Summary, in English


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.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Diabetes - Islet Patophysiology

Publishing year

2019

Language

English

Pages

10-20

Publication/Series

Islets

Volume

11

Issue

1

Document type

Journal article

Publisher

Landes Bioscience

Topic

  • Endocrinology and Diabetes

Keywords

  • Diabetes
  • gene expression microarray
  • human islets
  • INS-1 (832/13)
  • insulin secretion
  • Retinoic acid-related orphan receptor

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 1938-2014