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Tauroursodeoxycholate (TUDCA), chemical chaperone, enhances function of islets by reducing ER stress

Cited 57 time in Web of Science Cited 58 time in Scopus
Authors
Lee, Yeon Yi; Hong, Shin Hee; Lee, Ye Jin; Chung, Sung Soo; Park, Sang Gyu; Park, Kyong Soo; Jung, Hye Seung
Issue Date
2010-07-09
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS; Vol.397 4; 735-739
Keywords
Diabetes mellitusInsulinIsletsER stressApoptosis
Abstract
The exposure to acute or chronic endoplasmic reticulum (ER) stress has been known to induce dysfunction of islets, leading to apoptosis. The reduction of ER stress in islet isolation for transplantation is critical for islet protection. In this study, we investigated whether tauroursodeoxycholate (TUDCA) could inhibit ER stress induced by thapsigargin, and restore the decreased glucose stimulation index of islets. In pig islets, thapsigargin decreased the insulin secretion by high glucose stimulation in a time-dependent manner (1 h, 1.35 +/- 0.16: 2 h, 1.21 +/- 0.13; 4 h, 1.17 +/- 0.16 vs. 0 h, 1.81 +/- 0.15, n = 4, p < 0.05. respectively). However, the treatment of TUDCA restored the decreased insulin secretion index induced by thapsigargin (thapsigargin, 1.25 +/- 0.12 vs. thapsigargin + TUDCA, 2.13 +/- 0.19, n = 5, p < 0.05). Furthermore, the culture of isolated islets for 24 h with TUDCA significantly reduced the rate of islet regression (37.4 +/- 5.8% vs. 14.5 +/- 6.4%, n = 12, p < 0.05). The treatment of TUDCA enhanced ATP contents in islets (27.2 +/- 3.2 pmol/20IEQs vs. 21.7 +/- 2.8 pmol/20IEQs, n = 9, p < 0.05). The insulin secretion index by high glucose stimulation is also increased by treatment of TUDCA (2.42 +/- 0.15 vs. 1.92 +/- 0.12, n = 12, p < 0.05). Taken together, we suggest that TUDCA could be a useful agent for islet protection in islet isolation for transplantation. (C) 2010 Elsevier Inc. All rights reserved.
ISSN
0006-291X
Language
English
URI
http://hdl.handle.net/10371/76480
DOI
https://doi.org/10.1016/j.bbrc.2010.06.022
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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