1993 Fiscal Year Final Research Report Summary
Role of gene mutations in development of diabetes mellitus
| Project/Area Number |
04454563
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Kobe University |
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Principal Investigator |
KASUGA Masato Kobe University School of Medicine, Professor, 医学部, 教授 (50161047)
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| Co-Investigator(Kenkyū-buntansha) |
AOYAMA Nobuo Kobe University School of Medicine, Assistant Professor, 医学部, 助手 (30243299)
YOKONO Koichi Kobe University School of Medicine, Associate Professor, 医学部・附属病院, 講師 (50144580)
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| Project Period (FY) |
1992 – 1993
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| Keywords | insulin receptor gene / glucokinase gene / mitochondrial gene / IRS-1 gene / glucose transporter gene |
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| Research Abstract |
Mutations of insulin receptor gene, glucokinase gene, mitochaondrial gene and IRS-1 gene in diabetic parients were investigated. We found a mutation of insulin receptor gene in one family of insulin resistance and diabetes mellitus. We expressed this mutant insulin receptor gene in cultured cells and found that this mutation decreased kinase activity of insulin receptors and insulin action. We also found a mutation of glucokinase gene in one family of diabetes mellitus, however this mutation was aleady reportred in other family member by other investigators. We found a mutation (A to G transition at position 3243) of mitochondrial gene in several diabetic patients. These patients had several characteristics such as maternal inheritance, deafness, lean body constitutions, decreased insulin secretion in response to glucose and decreased glucagon secretion in response to arginine. We found a mutation of IRS-1 gene, however the frequency of this mutation was not changed between diabetic patients and control subjects suggesting this mutation may not be involved in the development of diabetes mellitus. We also examined mutations of glucose transporter genes and did not find any significant mutations. One purpose of this project is to clarify a role of mutation in the development of diabetes mellitus by expressing the mutant gene in cultured cells, however we only succeeded in expressing of the mutant insulin receptor gene into cultured cells. It will be necessary to express these mutants of genes in cultured cells or mice for understanding the pathogenesis of diabetes mellitus caused by gene mutations.
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[Publications] Kishimoto, M., Hashiramoto, M., Yonezawa, K., Shii, K., Kazumi, T.and Kasuga, M.: "Substitution of glutamine for arginine 1131 : A newly-identified mutation in the catalytic loop of the tyrosine kinase domain of the human insulin receptor." J.Biol.Chem.269. 11349-11355 (1994)
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[Publications] Yoshida, R., Ishida, Y., Hozumi, T., Ueno, H., Kishimoto, M.Kasuga, M.and Kazumi, T.: "Congestive heart failure in mitochondrial diabetes mellitus." Lancet (letter). 344. 1375 (1994)
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[Publications] Kishimoto, M., Hashiramoto, M., Araki, S., Ishida, Y., Kazumi, T., Kanda, F.and Kasuga, M.: "Diabetes mellitus carrying mutation in mitochondrial tRNALeu (UUR) gene." Diabetologia. 38. 193-200 (1995)
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[Publications] Ishida, Y., Ueno, H., Yoshida, R., Hozumi, T., Shiotani, H., Matsunaga, K., Kasuga, M.and Kazumi, T.: "Cardiac sympathetic nervous dysfunction in mitochondrial cardiomyopathy and diabetes." Diabetes Care. 18. 1312-1313 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Yoshida, R., Ishida, Y., Abo, K., Hozumi, T., Ueno, H., Shiotani, H., Kishimoto-Hashiramoto, M., Hashiramoto, M., Matsunaga, K., Kasuga, M.Kazumi, T.: "Hypertrophic cardiomyopathy in patients with diabetes mellitus associated with mitochondrial tRNALeu (UUR) gene mutation." Int.Med.34. 953-958 (1995)
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「研究成果報告書概要(欧文)」より
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