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DC Field | Value | Language |
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dc.citation.endPage | 586 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 571 | - |
dc.citation.title | DIABETES | - |
dc.citation.volume | 68 | - |
dc.contributor.author | Thoudam, Themis | - |
dc.contributor.author | Ha, Chae-Myeong | - |
dc.contributor.author | Leem, Jaechan | - |
dc.contributor.author | Chanda, Dipanjan | - |
dc.contributor.author | Park, Jong-Seok | - |
dc.contributor.author | Kim, Hyo-Jeong | - |
dc.contributor.author | Jeon, Jae-Han | - |
dc.contributor.author | Choi, Yeon-Kyung | - |
dc.contributor.author | Liangpunsakul, Suthat | - |
dc.contributor.author | Huh, Yang Hoon | - |
dc.contributor.author | Kwon, Tae-Hwan | - |
dc.contributor.author | Park, Keun-Gyu | - |
dc.contributor.author | Harris, Robert A. | - |
dc.contributor.author | Park, Kyu-Sang | - |
dc.contributor.author | Rhee, Hyun-Woo | - |
dc.contributor.author | Lee, In-Kyu | - |
dc.date.accessioned | 2023-12-21T19:21:48Z | - |
dc.date.available | 2023-12-21T19:21:48Z | - |
dc.date.created | 2019-03-11 | - |
dc.date.issued | 2019-03 | - |
dc.description.abstract | Mitochondria-associated endoplasmic reticulum membrane (MAM) is a structural link between mitochondria and endoplasmic reticulum (ER). MAM regulates Ca2+ transport from the ER to mitochondria via an IP3R1-GRP75-VDAC1 complex-dependent mechanism. Excessive MAM formation may cause mitochondrial Ca2+ overload and mitochondrial dysfunction. However, the exact implication of MAM formation in metabolic syndromes remains debatable. Here, we demonstrate that PDK4 interacts with and stabilizes the IP3R1-GRP75-VDAC1 complex at the MAM interface. Obesity-induced increase in PDK4 activity augments MAM formation and suppresses insulin signaling. Conversely, PDK4 inhibition dampens MAM formation and improves insulin signaling by preventing MAM-induced mitochondrial Ca2+ accumulation, mitochondrial dysfunction, and ER stress. Furthermore, Pdk4(-/-) mice exhibit reduced MAM formation and are protected against diet-induced skeletal muscle insulin resistance. Finally, forced formation and stabilization of MAMs with synthetic ER-mitochondria linker prevented the beneficial effects of PDK4 deficiency on insulin signaling. Overall, our findings demonstrate a critical mediatory role of PDK4 in the development of skeletal muscle insulin resistance via enhancement of MAM formation. | - |
dc.identifier.bibliographicCitation | DIABETES, v.68, no.3, pp.571 - 586 | - |
dc.identifier.doi | 10.2337/db18-0363 | - |
dc.identifier.issn | 0012-1797 | - |
dc.identifier.scopusid | 2-s2.0-85061924930 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/26163 | - |
dc.identifier.url | http://diabetes.diabetesjournals.org/content/68/3/571 | - |
dc.identifier.wosid | 000459677400011 | - |
dc.language | 영어 | - |
dc.publisher | AMER DIABETES ASSOC | - |
dc.title | PDK4 Augments ER-Mitochondria Contact to Dampen Skeletal Muscle Insulin Signaling During Obesity | - |
dc.type | Article | - |
dc.description.isOpenAccess | FALSE | - |
dc.relation.journalWebOfScienceCategory | Endocrinology & Metabolism | - |
dc.relation.journalResearchArea | Endocrinology & Metabolism | - |
dc.type.docType | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | ENDOPLASMIC-RETICULUM-STRESS | - |
dc.subject.keywordPlus | MEMBRANE MAM INTEGRITY | - |
dc.subject.keywordPlus | DYSFUNCTION | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | CA2+ | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | CONTRIBUTES | - |
dc.subject.keywordPlus | DISRUPTION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | RELEASE | - |
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