Regulation of Pancreatic β Cell Mass by Cross-Interaction between CCAAT Enhancer Binding Protein β Induced by Endoplasmic Reticulum Stress and AMP-Activated Protein Kinase Activity.

التفاصيل البيبلوغرافية
العنوان:	Regulation of Pancreatic β Cell Mass by Cross-Interaction between CCAAT Enhancer Binding Protein β Induced by Endoplasmic Reticulum Stress and AMP-Activated Protein Kinase Activity.
المؤلفون:	Tomokazu Matsuda, Hiroaki Takahashi, Yusuke Mieda, Shinobu Shimizu, Takeshi Kawamoto, Yuki Matsuura, Tomoko Takai, Emi Suzuki, Ayumi Kanno, Maki Koyanagi-Kimura, Shun-ichiro Asahara, Alberto Bartolome, Norihide Yokoi, Hiroshi Inoue, Wataru Ogawa, Susumu Seino, Yoshiaki Kido
المصدر:	PLoS ONE, Vol 10, Iss 6, p e0130757 (2015)
بيانات النشر:	Public Library of Science (PLoS), 2015.
سنة النشر:	2015
المجموعة:	LCC:Medicine LCC:Science
مصطلحات موضوعية:	Medicine, Science
الوصف:	During the development of type 2 diabetes, endoplasmic reticulum (ER) stress leads to not only insulin resistance but also to pancreatic beta cell failure. Conversely, cell function under various stressed conditions can be restored by reducing ER stress by activating AMP-activated protein kinase (AMPK). However, the details of this mechanism are still obscure. Therefore, the current study aims to elucidate the role of AMPK activity during ER stress-associated pancreatic beta cell failure. MIN6 cells were loaded with 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) and metformin to assess the relationship between AMPK activity and CCAAT enhancer binding protein β (C/EBPβ) expression levels. The effect of C/EBPβ phosphorylation on expression levels was also investigated. Vildagliptin and metformin were administered to pancreatic beta cell-specific C/EBPβ transgenic mice to investigate the relationship between C/EBPβ expression levels and AMPK activity in the pancreatic islets. When pancreatic beta cells are exposed to ER stress, the accumulation of the transcription factor C/EBPβ lowers the AMP/ATP ratio, thereby decreasing AMPK activity. In an opposite manner, incubation of MIN6 cells with AICAR or metformin activated AMPK, which suppressed C/EBPβ expression. In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBPβ transgenic mice decreased C/EBPβ expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity. Enhanced C/EBPβ expression and decreased AMPK activity act synergistically to induce ER stress-associated pancreatic beta cell failure.
نوع الوثيقة:	article
وصف الملف:	electronic resource
اللغة:	English
تدمد:	1932-6203
Relation:	http://europepmc.org/articles/PMC4474801?pdf=render; https://doaj.org/toc/1932-6203
DOI:	10.1371/journal.pone.0130757
URL الوصول:	https://doaj.org/article/8b5e6be2e4a64e57bed35e4a3c13a23d
رقم الانضمام:	edsdoj.8b5e6be2e4a64e57bed35e4a3c13a23d
قاعدة البيانات:	Directory of Open Access Journals

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الوصف
تدمد:	19326203
DOI:	10.1371/journal.pone.0130757