Tauroursodeoxycholate (TUDCA), chemical chaperone, enhances function of islets by reducing ER stress |
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Authors: | Yeon Yi Lee Shin Hee Hong Ye Jin Lee Sung Soo Chung Hye Seung Jung Sang Gyu Park Kyong Soo Park |
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Affiliation: | a Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Republic of Korea b Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Republic of Korea c Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea d Department of Biomedical Science, CHA University, Yeoksamdong, Kangnamgu, Seoul, Republic of Korea e Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea |
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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. |
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Keywords: | TUDCA, tauroursodeoxycholate ER, endoplasmic reticulum JNK, c-Jun N-terminal kinase GSIR, glucose-stimulated insulin release DAPI, diamidino-2-phenylindole |
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