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

Hyun Seok Jin; Jeonghyun Kim; Soo Jin Lee; Kyunga Kim; Min Jin Go; Jong Young Lee; Hye Ja Lee; Jihyun Song; Byeong Tak Jeon; Gu Seob Roh; Sung Jun Kim; Bo Young Kim; Kyung Won Hong; Young Hyun Yoo; Beomseok Oh; Yup Kang; Seon Yong Jeong

doi:10.1016/j.mce.2013.09.031

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

Hyun Seok Jin, Jeonghyun Kim, Soo Jin Lee, Kyunga Kim, Min Jin Go, Jong Young Lee, Hye Ja Lee, Jihyun Song, Byeong Tak Jeon, Gu Seob Roh, Sung Jun Kim, Bo Young Kim, Kyung Won Hong, Young Hyun Yoo, Beomseok Oh, Yup Kang, Seon Yong Jeong

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

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=~1.2×10^-4) and insulin secretion indices (p=~7.4×10^-5) in male KARE subjects. Parkin was expressed predominantly in the rat pancreatic islets. Downregulation of the Park2 gene in rat INS-1 β-cells resulted in a significant decrease in the glucose-stimulated insulin secretion, intracellular insulin gene expression, and intracellular ATP level. The Park2-depleted β-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 β-cell function.

Original language	English
Pages (from-to)	178-189
Number of pages	12
Journal	Molecular and Cellular Endocrinology
Volume	382
Issue number	1
DOIs	https://doi.org/10.1016/j.mce.2013.09.031
Publication status	Published - 25 Jan 2014

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korean government ( 2009-0093189, 2012-051426, and 2012R1A1A2009459 ).

Keywords

Genetic association
Insulin secretion
Mitochondria
PARK2
Pancreatic β-cell
Type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.mce.2013.09.031

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Jin, H. S., Kim, J., Lee, S. J., Kim, K., Go, M. J., Lee, J. Y., Lee, H. J., Song, J., Jeon, B. T., Roh, G. S., Kim, S. J., Kim, B. Y., Hong, K. W., Yoo, Y. H., Oh, B., Kang, Y., & Jeong, S. Y. (2014). The PARK2 gene is involved in the maintenance of pancreatic β-cell functions related to insulin production and secretion. Molecular and Cellular Endocrinology, 382(1), 178-189. https://doi.org/10.1016/j.mce.2013.09.031

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

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=~1.2×10-4) and insulin secretion indices (p=~7.4×10-5) in male KARE subjects. Parkin was expressed predominantly in the rat pancreatic islets. Downregulation of the Park2 gene in rat INS-1 β-cells resulted in a significant decrease in the glucose-stimulated insulin secretion, intracellular insulin gene expression, and intracellular ATP level. The Park2-depleted β-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 β-cell function.",

keywords = "Genetic association, Insulin secretion, Mitochondria, PARK2, Pancreatic β-cell, Type 2 diabetes",

author = "Jin, {Hyun Seok} and Jeonghyun Kim and Lee, {Soo Jin} and Kyunga Kim and Go, {Min Jin} and Lee, {Jong Young} and Lee, {Hye Ja} and Jihyun Song and Jeon, {Byeong Tak} and Roh, {Gu Seob} and Kim, {Sung Jun} and Kim, {Bo Young} and Hong, {Kyung Won} and Yoo, {Young Hyun} and Beomseok Oh and Yup Kang and Jeong, {Seon Yong}",

note = "Funding Information: This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korean government ( 2009-0093189, 2012-051426, and 2012R1A1A2009459 ). ",

year = "2014",

month = jan,

day = "25",

doi = "10.1016/j.mce.2013.09.031",

language = "English",

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Jin, HS, Kim, J, Lee, SJ, Kim, K, Go, MJ, Lee, JY, Lee, HJ, Song, J, Jeon, BT, Roh, GS, Kim, SJ, Kim, BY, Hong, KW, Yoo, YH, Oh, B, Kang, Y & Jeong, SY 2014, 'The PARK2 gene is involved in the maintenance of pancreatic β-cell functions related to insulin production and secretion', Molecular and Cellular Endocrinology, vol. 382, no. 1, pp. 178-189. https://doi.org/10.1016/j.mce.2013.09.031

TY - JOUR

T1 - The PARK2 gene is involved in the maintenance of pancreatic β-cell functions related to insulin production and secretion

AU - Jin, Hyun Seok

AU - Kim, Jeonghyun

AU - Lee, Soo Jin

AU - Kim, Kyunga

AU - Go, Min Jin

AU - Lee, Jong Young

AU - Lee, Hye Ja

AU - Song, Jihyun

AU - Jeon, Byeong Tak

AU - Roh, Gu Seob

AU - Kim, Sung Jun

AU - Kim, Bo Young

AU - Hong, Kyung Won

AU - Yoo, Young Hyun

AU - Oh, Beomseok

AU - Kang, Yup

AU - Jeong, Seon Yong

N1 - Funding Information: This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korean government ( 2009-0093189, 2012-051426, and 2012R1A1A2009459 ).

PY - 2014/1/25

Y1 - 2014/1/25

N2 - 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=~1.2×10-4) and insulin secretion indices (p=~7.4×10-5) in male KARE subjects. Parkin was expressed predominantly in the rat pancreatic islets. Downregulation of the Park2 gene in rat INS-1 β-cells resulted in a significant decrease in the glucose-stimulated insulin secretion, intracellular insulin gene expression, and intracellular ATP level. The Park2-depleted β-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 β-cell function.

AB - 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=~1.2×10-4) and insulin secretion indices (p=~7.4×10-5) in male KARE subjects. Parkin was expressed predominantly in the rat pancreatic islets. Downregulation of the Park2 gene in rat INS-1 β-cells resulted in a significant decrease in the glucose-stimulated insulin secretion, intracellular insulin gene expression, and intracellular ATP level. The Park2-depleted β-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 β-cell function.

KW - Genetic association

KW - Insulin secretion

KW - Mitochondria

KW - PARK2

KW - Pancreatic β-cell

KW - Type 2 diabetes

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U2 - 10.1016/j.mce.2013.09.031

DO - 10.1016/j.mce.2013.09.031

M3 - Article

C2 - 24096089

AN - SCOPUS:84885817939

SN - 0303-7207

VL - 382

SP - 178

EP - 189

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

IS - 1

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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