2006 Fiscal Year Final Research Report Summary
Metabolic pathway altered in the liver of patients with type 2 diabetes and its regulation
| Project/Area Number |
17590920
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kanazawa University |
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Principal Investigator |
TAKAMURA Toshinari Graduate School of Medical Science, Associate Professor, 医学系研究科, 助教授 (00324111)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Diabetes / Gene / Microarray / Biomolecule / Nutrition |
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| Research Abstract |
Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes for OXPHOS have been reported to be down-regulated in the skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown.
In the present study, I analyzed gene expression for OXPHOS from the livers of 14 patients with type 2 diabetes and 14 subjects with normal glucose tolerance (NGT) using serial analysis of gene expression (SAGE) and DNA chip analysis. I evaluated the correlation between gene expression levels for OXPHOS and clinical parameters of individuals with type 2 diabetes and NGT.
Both gene analyses showed that genes for OXPHOS were significantly up-regulated in the type 2 diabetic liver.
In the SAGE analysis, tag count comparisons of mitochondrial transcripts showed that rRNAs were 3.5-fold over-expressed, and mRNAs were 1.2-fold over-expressed in the type 2 diabetes library. DNA chip analysis revealed that gene expression for OXPHOS, which correlated with several nuclear factors, including estrogen-related receptor-a (ERR-α) or peroxisome proliferator-activated receptor-y (PPAR-y), was a predictor of fasting plasma glucose levels, independent of age, body mass index, insulin resistance, and fasting insulin levels (P=0.04). Surprisingly, genes for OXPHOS did not correlate with either peroxisome proliferator-activated receptor-γ coactivator-la (PGC-1α) or nuclear respiratory factor 1 (NRF-1).
These results indicate that up-regulated genes for OXPHOS in the liver, which are regulated by different mechanisms from genes in the skeletal muscle, are associated with fasting hyperglycemia in patients with type 2 diabetes.
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[Journal Article] Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes2007
Author(s)
Misu H, Takamura T, Matsuzawa N, Shimizu A, Ota T, Sakurai M, Ando H, Arai K, Yamashita T, Honda M, Yamashita T. Kaneko S
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Journal Title
Diabetologia 50
Pages: 268-277
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Insulin resistance accelerates a dietary rat model of nonalcoholic steatohepatitis2007
Author(s)
Ota T, Takamura T, Kurita S, Matsuzawa N, Kita Y, Uno M, Akahori H, Misu H, Sakurai M, Zen Y, Nakanuma Y, Kaneko S
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Journal Title
Gastroenterology 132
Pages: 282-293
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Factors associated with improvement of fasting plasma glucose level by mealtime dosing of a rapid-acting insulin analog in type 2 diabetes2007
Author(s)
Takamura T, Sakurai M, Nakamura M, Shimizu A, Ota T, Misu H, Takeshita Y, Tsuchiyama N, Kurita S, Ando H, Kaneko S
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Journal Title
Diabetes Res Clin Pract 75
Pages: 278-284
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pancreatic exocrine and endocrine events occur concomitantly but independently during the course of fulminant type 1 diabetes2006
Author(s)
Kahara T, Takamura T, Sakurai M, Misu H, Usuda R, Hayakawa T, Nishimura Y, Bando Y, Nagaoka T, Nagai Y, Kaneko S
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Journal Title
Diabetes Res Clin Pract 71
Pages: 241-246
Description
「研究成果報告書概要(欧文)」より
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