1990 Fiscal Year Final Research Report Summary
Study on the Pathogenesis of Type 1 Diabetes Mellitus
| Project/Area Number |
01480290
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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 | Osaka University |
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Principal Investigator |
HANAFUSA Toshiaki Osaka University Medical School, 医学部, 助手 (60164886)
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| Co-Investigator(Kenkyū-buntansha) |
宮川 潤一郎 大阪大学, 医学部・附属病院, 医員
KONO Norio Osaka University Medical School, 医学部, 講師 (30093412)
MIYAGAWA Junーichiro Osaka University Medical School Hospital
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| Project Period (FY) |
1989 – 1990
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| Keywords | Type 1 diabetes / MHC antigens / Cytokines / Interferon-gamma / Pancreatic beta cells / Pathogenesis / Insulin secretion / Molecular biology |
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| Research Abstract |
The pathogenic role of abnormal expression of major histocompatibility complex (MHC) antigens on pancreatic beta cells was studied using molecular biological techniques.
We first tested which cytokines could induce MHC antigen expression on rat insulinoma cell line RINm5F. Messenger RNAs of class I and class II MHC molecules were examined by Northern analysis. The result showed that, in the absence of cytokines, 1) class I MHC antigen mRNA was constitutively expressed but 2) class II MHC mRNA was not detected in RINm5F cells. Class I mRNA was increased in response to either interferonーgamma (IFNgamma) or IFNgamma plus tumor necrosis factorーalpha (TNFalpha). However, no class II mRNA was detected after the challenge of any cytokines. On the other hand, insulin mRNA was decreased in the presence of either IFNgamma or IFNgamma+TNFalpha.
We secondly examined the effect of MHC antigen expression on beta cell function, namely insulin secreting capacity. RINm5F cells were transfected with human MHC class I antigen (HLA-Cw2) gene and twelve clones with different degrees of expression of the transfectant were obtained. Insulin secreting capacity of the clones in response to glucose was negatively correlated with the amount of class I MHC antigen expressed.
These results indicate that the expression of MHC antigen in beta cells is controlled by various cytokines and that insulin secreting capacity is impaired by the expression of MHC antigens in beta cells. This suggests the importance of MHC antigen expression in the pathogenesis of Type 1 diabetes mellitus.
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Research Products
(15 results)
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[Publications] Hanafusa T, Miyazaki A, Miyagawa J, Tamura S, Inada M, Yamada K, Shinji Y, Katsura H, Yamagata K, Itoh N, Asakawa H, Nakagawa C, Otsuka A, Kawata S, Kono N, Tarui S: "Examination of islets in the pancreas biopsy specimens from newly diagnosed Type 1 (insulinーdependent) diabetic patients." Diabetologia. 33(2). 105-111 (1990)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Asakawa H, Miyagawa J, Hanafusa T, Katsura H, Miyazaki A, Otsuka A, Nakagawa C, Yamagata K, Tajima K, Mashita K, Kono N, Tarui S: "Interferonーgamma reduces actin filaments and inhibits thyroidーstimulating hormoneーinduced formation of microvilli and pseudopods in mouse monolayer thyrocytes." Endocrinology. 127(1). 325-329 (1990)
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「研究成果報告書概要(欧文)」より
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[Publications] Miyagawa J, Yamamoto K, Hanafusa T, Itoh N, Nakagawa C, Otsuka A, Katsura H, Yamagata K, Miyazaki A, Kono N, Tarui S: "Preventive effect of a new immunosuppressant FK-506 on insulitis and diabetes in nonーobese diabetic mice." Diabetologia. 33(8). 503-505 (1990)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamagata K, Hanafusa T, Nakajima H, Miyagawa J, Miyazaki A, Kono N, Tarui S: "Expression of MHC antigens on islet cells in insulinーdependent diabetes mellitus : analysis of pancreas biopsy specimens and RINm5F cells," Recent Trends of Diabetes Mellitus in East Asia, eds Mimura G, Zhisheng C, Elsevier Science Publishers B. V., Amsterdam. 69-72 (1990)
Description
「研究成果報告書概要(欧文)」より
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