A New Gene Contributes to Diabetes and Affects Glucose Metabolism

Abstract

Introduction and Study Objective: Type 2 diabetes is a multifactorial and gene disease. More than 140 genetic variants linked to the cause of the disease have been detected, but they only explain 10% of the genetic causes of diabetes. Therefore, this study seeks to use a new approach in which new genes are identified involved in the physiology of diabetes and insulin secretion. Research Method: RNA sequencing data from human pancreatic islands was analyzed and collected from 89 donors. A series of functional trials were also conducted in animal beta cells (INS-1) of mice to investigate the potential role of the candidate gene including inhibition of its activity, insulin secretion, cell vitality, programmed cell death, and gene expression. Results: Differential gene expression analysis of RNA sequence data showed that 231 genes had significantly lower expression in pancreatic islands from diabetes donors compared to healthy people. The number of genes was reduced to 37 due to the application of stricter statistical pieces. Among those genes, PPP1R1A was selected as a candidate gene because of its strong association with cumulative diabetes, and its high gene expression in human pancreatic islands compared to other genes. Also, the expression of important functional genes in beta cells such as INS, PDX1, GLUT2 and INR was found to have decreased significantly in cells where PPP1R1A activity was inhibited. The study concluded that PPP1R1A is a gene regulating the function of beta cells and insulin secretion, and highlighted a list of genes that may have a role and effect in diabetes.