a Sharjah Institute for Medical Research , University of Sharjah , Sharjah , UAE.
b Department of Clinical Science, Division of Islet Cell Physiology , Lund University , Malmö , Sweden.
Islets. 2019;11(1):10-20. doi: 10.1080/19382014.2019.1566684. Epub 2019 Feb 14.
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 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, that of RORC correlated negatively with HbA. 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.
关于维甲酸相关孤儿受体（RORA、B 和 C）在胰腺β细胞中的表达和功能知之甚少。在这里，我们利用 cDNA 微阵列和 RNA 测序方法研究了正常和糖尿病人类胰岛中 ROR 受体的表达模式。评估了 RORs 表达与 HbA 水平以及分离的人类胰岛中胰岛素分泌能力之间的可能相关性。还验证了 RORB 和 RORC 表达对 INS-1（832/13）细胞胰岛素分泌的影响。虽然 RORA 是人类胰岛细胞中三种 ROR 中表达最高的基因，但 RORC 是 INS-1 细胞（832/13）中表达最高的基因，而 RORB 是人类胰岛细胞中表达最低的基因，RORA 是 INS-1 细胞（832/13）中表达最高的基因。与非糖尿病对照组相比，糖尿病/高血糖供体的 RORB 和 RORC 表达显着降低。此外，虽然 RORB 的表达与胰岛素分泌呈正相关，与 HbA 呈负相关，但 RORC 的表达与 HbA 呈负相关。RORA 的表达模式与这两个参数均不相关。siRNA 沉默 INS-1（832/13）细胞中的 RORB 或 RORC 导致胰岛素 mRNA 表达和胰岛素分泌显着下调。这些发现表明 RORB 和 RORC 是调节胰腺β细胞胰岛素分泌的分子级联的一部分；为进一步研究 RORB 和 RORC 基因在 2 型糖尿病β细胞功能障碍中的潜在治疗用途提供了依据。
