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Overexpression of short heterodimer partner recovers impaired glucose-stimulated insulin secretion of pancreatic β-cellsoverexpressing UCP2

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Author(s)
Y-H SuhS-Y KimH-Y LeeB C JangJ H BaeJ-N SohnJ-H BaeS-I SuhJ-W ParkK-U LeeD-K Song
Keimyung Author(s)
Bae, Jae HoonSuh, Seong IlPark, Jong WookSong, Dae Kyu
Department
Dept. of Physiology (생리학)
Dept. of Immunology (면역학)
Dept. of Microbiology (미생물학)
Journal Title
Journal of Endocrinology
Issued Date
2004
Volume
183
Issue
1
Abstract
The short heterodimer partner (SHP) (NR0B2) is an orphan nuclear receptor whose function in pancreatic β-cells is unclear. Mitochondrial uncoupling protein (UCP2) in β-cells is upregulated in obesity-related diabetes, causing impaired glucose-stimulated insulin secretion (GSIS). We investigated whether SHP plays a role in UCP2-induced GSIS impairment. We overexpressed SHP in normal islet cells and in islet cells overexpressing UCP2 by an adenovirus-mediated infection technique. We found that SHP overexpression enhanced GSIS in normal islets, and restored GSIS in UCP2-overexpressing islets. SHP overexpression increased the glucose sensitivity of ATP-sensitive K+ (KATP) channels and enhanced theATP/ADP ratio. A peroxisome proliferator-activated receptor gamma (PPARγ) antagonist, GW9662, did not block the SHP effect on GSIS. SHP overexpression also corrected the impaired sensitivity of UCP2-overexpressing β-cells to methylpyruvate, another energy fuel that bypasses glycolysis and directly enters the Krebs cycle. KATP channel inhibition mediated by dihydroxyacetone, which gives reducing equivalents directly to complex II of the electron transport system, was similar in Ad-Null-, Ad-UCP2- and Ad-UCP2+Ad-SHP-infected cells. The mitochondrial metabolic inhibitor sodium azide totally blocked the effect of SHP overexpression on GSIS. These results suggest that SHP positively regulates GSIS in β-cells and restores glucose sensitivity in UCP2-overexpressing β-cells by enhancing mitochondrial glucose metabolism, independent of PPARγ activation.
Keimyung Author(s)(Kor)
배재훈
서성일
박종욱
송대규
Publisher
School of Medicine
Citation
Y-H Suh et al. (2004). Overexpression of short heterodimer partner recovers impaired glucose-stimulated insulin secretion of pancreatic β-cellsoverexpressing UCP2. Journal of Endocrinology, 183(1), 133–144. doi: 10.1677/joe.1.05675
Type
Article
ISSN
0022-0795
DOI
10.1677/joe.1.05675
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33776
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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