Tauroursodeoxycholate (TUDCA), chemical chaperone, enhances function of islets by reducing ER stress.
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 (1h, 1.35+/-0.16; 2h, 1.21+/-0.13; 4h, 1.17+/-0.16 vs. 0h, 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 24h 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+/-3.2pmol/20IEQs vs. 21.7+/-2.8pmol/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.
Lee
Yeon Yi
YY
Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Republic of Korea.
Hong
Shin Hee
SH
Lee
Ye Jin
YJ
Chung
Sung Soo
SS
Jung
Hye Seung
HS
Park
Sang Gyu
SG
Park
Kyong Soo
KS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019610:Cytoprotection; D004721:Endoplasmic Reticulum / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D013312:Stress, Physiological / Q000187:drug effects*; D013552:Swine; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
D007328:Insulin; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D000255:Adenosine Triphosphate; D005947:Glucose