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The role of c-Myc dependent pathway in insulin resistance uncovered by integrative analysis of skeletal muscle transcriptome : 골격근 전사체 통합분석을 통해 발견한 c-Myc의 인슐린 저항성 조절 인자로서의 기능에 대한 연구
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 박경수 | - |
dc.contributor.author | 온정헌 | - |
dc.date.accessioned | 2017-07-14T01:51:23Z | - |
dc.date.available | 2017-07-14T01:51:23Z | - |
dc.date.issued | 2015-08 | - |
dc.identifier.other | 000000049827 | - |
dc.identifier.uri | https://hdl.handle.net/10371/122406 | - |
dc.description | 학위논문 (박사)-- 서울대학교 융합과학기술대학원 : 분자의학 및 바이오제약학과, 2015. 8. 박경수. | - |
dc.description.abstract | I aim to identify a novel pathway to regulate insulin resistance from transcriptional profiles of skeletal muscles from patients with diabetes and to demonstrate its role in experimental models of insulin resistance. I performed transcriptional profiling of skeletal muscles from subjects with or without diabetes. Through an integrative analysis of the dataset with four previous datasets, I identified the core gene sets associated with insulin resistance. Among the 46 core gene sets for transcriptional regulators, I focused on c-Myc with the highest regulatory power in the network of the core gene sets. c-Myc expression decreased in skeletal muscle from diet-induced obesity rodent model. In C2C12 myotubes, c-Myc transcriptional activity was decreased by palmitate or TNFα treatment inducing insulin resistance. Knockdown of c-Myc decreased expression of oxidative phosphorylation (OXPHOS) genes and PGC-1-related coactivator, but showed no change in PGC1α. ERK regulated c-Myc induction by insulin, and palmitate abrogated insulin-induced c-Myc expression by modulating ERK activation. These data demonstrate that ERK-c-Myc pathway regulates OXPHOS gene expression in skeletal muscle insulin resistance, independent of PGC1α. The unbiased integrative approach of transcriptional profiles revealed ERK-c-Myc pathway as a novel pathway for skeletal muscle insulin resistance. | - |
dc.description.tableofcontents | ABSTRACT
LIST OF FIGURES LIST OF TABLES Chapter I. Gene Set Enrichment Analysis-based Integrative Microarray Data Analysis Introduction Materials and methods Results Discussion Chapter II. c-Myc Dependent Pathway in Skeletal Muscle Insulin Resistance Introduction Materials and methods Results Discussion References 국문 초록 | - |
dc.format | application/pdf | - |
dc.format.extent | 2736005 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 융합과학기술대학원 | - |
dc.subject | c-Myc | - |
dc.subject | insulin resistance | - |
dc.subject | integrative microarray analysis | - |
dc.subject | mitochondria | - |
dc.subject | oxidative phosphorylation | - |
dc.subject.ddc | 610 | - |
dc.title | The role of c-Myc dependent pathway in insulin resistance uncovered by integrative analysis of skeletal muscle transcriptome | - |
dc.title.alternative | 골격근 전사체 통합분석을 통해 발견한 c-Myc의 인슐린 저항성 조절 인자로서의 기능에 대한 연구 | - |
dc.type | Thesis | - |
dc.description.degree | Doctor | - |
dc.citation.pages | vi, 88 | - |
dc.contributor.affiliation | 융합과학기술대학원 분자의학 및 바이오제약학과 | - |
dc.date.awarded | 2015-08 | - |
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