Molecular and Cellular Endocrinology, 2014, 01, 178─189

The PARK2 gene is involved in the maintenance of pancreatic β-cell functions related to insulin production and secretion

Jin HS, Kim J, Lee SJ, Go MJ, Lee JY Jeong SY

Abstract

Several association studies have implicated the PARK2 gene that encodes parkin ？ the key molecule orchestrating the mitochondrial quality control system ？ as a candidate susceptibility gene for diabetes. A total of 7551 unrelated Korean KARE cohort subjects were analyzed to investigate the association between the PARK2 single nucleotide polymorphism (SNP) and quantitative glycemic traits. Two SNPs, rs10455889 and rs9365294, were significantly associated with fasting plasma glucose level (p = ~1.2E-04) and insulin secretion indices (p = ~7.4E-05) in male KARE subjects. Parkin was expressed predominantly in the rat pancreatic islets. Downregulation of the Park2 gene in rat INS-1 b-cells resulted in a significant decrease in the glucose-stimulated insulin secretion, intracellular insulin gene expression, and intracellular ATP level. The Park2-depleted b-cells also exhibited increased mitochondrial fragmentation and ROS production and decreased mitochondrial membrane potential. Both population-based statistical evaluation and experimental evidence demonstrated a fundamental role of the PARK2 gene in the maintenance of b-cell function.

• ISBN or ISSN: 0303-7207

• 본 연구는 질병관리본부 연구개발과제(과제번호 2012-N73002-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2012-N73002-00) by Research of Korea Centers for Disease Control and Prevention.