Role of PARK2Gene in Maintenance of Pancreatic Beta Cell Functions
type: CreativeWork
description: Type 2 diabetes (T2D) is characterized by decreased insulin secretion and action. Although many studies have reported the genetic loci/genes for susceptibility to T2D, the vast majority of genetic factors in T2D are still unknown. Mitophagy, a selective elimination system for impaired mitochondria, plays a key role in mitochondrial quality control. Defects in mitophagy that contribute to causing mitochondrial dysfunction have been recently suggested to be involved in the pathogenesis of T2D as well as in neurodegenerative diseases. By performing a candidate-gene association analysis of the single nucleotide polymorphisms (SNPs) in the 28 mitophagy-related genes with glucose- and insulin-related quantitative traits in the Korean study cohort (7,551 subjects), I found that two SNPs, rs10455889 and rs9365294, in the PARK2 gene encoding an E3 ubiquitin-protein ligase (parkin) were significantly associated with fasting plasma glucose levels and insulin secretion indices in response to glucose stimulation in men (3,747 subjects). Replication analysis in two other Korean cohorts and a European-descendent cohort revealed that genetic variants in the PARK2 gene were associated with glucose homeostasis-related quantitative traits in three cohorts. One variant showed a meaningful linkage disequilibrium correlation to the two discovered PARK2 SNPs. The PARK2 gene is known to be mutated in certain cases of familial Parkinson’s disease. Nevertheless, my results indicated a close relationship between the PARK2 gene and pancreatic β-cell dysfunction-related T2D. In order to prove this finding experimentally, I first investigated whether the PARK2 gene is expressed in the pancreatic tissues. Gene expression profiling of the Park2 gene in rats showed its predominant expression in the pancreatic islets as well as in the brain, skeletal muscle, and liver tissues. Next, I performed a functional analysis to investigate whether the alterations in PARK2 gene expression have an influence on…
abstract: Type 2 diabetes (T2D) is characterized by decreased insulin secretion and action. Although many studies have reported the genetic loci/genes for susceptibility to T2D, the vast majority of genetic factors in T2D are still unknown. Mitophagy, a selective elimination system for impaired mitochondria, plays a key role in mitochondrial quality control. Defects in mitophagy that contribute to causing mitochondrial dysfunction have been recently suggested to be involved in the pathogenesis of T2D as well as in neurodegenerative diseases. By performing a candidate-gene association analysis of the single nucleotide polymorphisms (SNPs) in the 28 mitophagy-related genes with glucose- and insulin-related quantitative traits in the Korean study cohort (7,551 subjects), I found that two SNPs, rs10455889 and rs9365294, in the PARK2 gene encoding an E3 ubiquitin-protein ligase (parkin) were significantly associated with fasting plasma glucose levels and insulin secretion indices in response to glucose stimulation in men (3,747 subjects). Replication analysis in two other Korean cohorts and a European-descendent cohort revealed that genetic variants in the PARK2 gene were associated with glucose homeostasis-related quantitative traits in three cohorts. One variant showed a meaningful linkage disequilibrium correlation to the two discovered PARK2 SNPs. The PARK2 gene is known to be mutated in certain cases of familial Parkinson’s disease. Nevertheless, my results indicated a close relationship between the PARK2 gene and pancreatic β-cell dysfunction-related T2D. In order to prove this finding experimentally, I first investigated whether the PARK2 gene is expressed in the pancreatic tissues. Gene expression profiling of the Park2 gene in rats showed its predominant expression in the pancreatic islets as well as in the brain, skeletal muscle, and liver tissues. Next, I performed a functional analysis to investigate whether the alterations in PARK2 gene expression have an influence on…
author: 김, 정현
language: en
keywords: genetic association, single nucleotide polymorphism (SNP), mitochondrial dysfunction, mitochondrial quality control, mitophagy, PARK2, parkin, fasting blood glucose, insulin secretion, pancreatic β-cell, type 2 diabetes, 연관성 분석, 단일염기 다형성(SNP), 미토콘드리아 기능 이상, 미토콘드리아 질 조절, 미토콘드리아성 자가포식, 공복 시 혈당, 인슐린 분비, 췌장 베타-세포, 제 2 형 당뇨병
date published: 2014-11-11T06:55:39Z
date modified: 2026-07-24T00:51:44Z
provider: Ajou University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Ajou University