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

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:382

Article

Jin, Hyun-Seok¹  Kim, Jeonghyun¹  Lee, Soo-Jin²  Kim, Kyunga³  Go, Min Jin⁴  Lee, Jong-Young⁴  Lee, Hye-Ja⁵  Song, Jihyun⁵  Jeon, Byeong Tak⁶  Roh, Gu Seob⁶  Kim, Sung-Jun⁷  Kim, Bo-Young¹  Hong, Kyung-Won⁸  Yoo, Young-Hyun^9,10  Oh, Beomseok¹¹  Kang, Yup²  Jeong, Seon-Yong¹ 

[1] Ajou Univ, Sch Med, Dept Med Genet, Suwon 443721, South Korea

[2] Ajou Univ, Sch Med, Inst Med Sci, Suwon 441749, South Korea

[3] Sookmyung Womens Univ, Dept Stat, Seoul, South Korea

[4] Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea

[5] Natl Inst Hlth, Ctr Biomed Sci, Div Metab Dis, Chungcheongbuk Do, South Korea

[6] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Dept Anat & Neurobiol, Jinju, South Korea

[7] CJ CheilJedang Corp, Drug Evaluat Ctr, Inchon, South Korea

[8] Korea Ctr Dis Control & Prevent, Ctr Genome Sci, Div Epidemiol & Hlth Index, Chungcheongbuk Do, South Korea

[9] Dong A Univ, Coll Med, Dept Anat & Cell Biol, Pusan, South Korea

[10] Dong A Univ, Coll Med, Mitochondria Hub Regulat Ctr, Pusan, South Korea

[11] Kyung Hee Univ, Sch Med, Dept Biomed Engn, Seoul, South Korea

关键词: Type 2 diabetes;    Pancreatic beta-cell;    Insulin secretion;    Genetic association;    PARK2;    Mitochondria;   

DOI  :  10.1016/j.mce.2013.09.031

来源: Elsevier

【 摘 要 】

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 = similar to 1.2 x 10(-4)) and insulin secretion indices (p = similar to 7.4 x 10(-5)) in male KARE subjects. Parkin was expressed predominantly in the rat pancreatic islets. Downregulation of the Park2 gene in rat INS-1 beta-cells resulted in a significant decrease in the glucose-stimulated insulin secretion, intracellular insulin gene expression, and intracellular ATP level. The Park2-depleted beta-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 beta-cell function. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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