2013 Fiscal Year Final Research Report
The role of protein kinase C pathway on mineralocorticoid receptor activation in resistant hypertension associated with diabetes mellitus
| Project/Area Number |
24790855
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
JO Rie 慶應義塾大学, 医学部, 助教 (30464861)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | ミネラルコルチコイド受容体 / アルドステロン / 糖尿病 / プロテインキナーゼC / 高血圧 |
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| Research Abstract |
Protein kinase C (PKC) pathway is known to be strongly associated with the development of diabetic complications. In this study, we showed for the first time that the activation of PKC pathway in high glucose condition induces mineralocorticoid receptor (MR) activation, which develops resistant hypertension and diabetic complications. This finding may partly account for the efficacy of PKC-beta inhibitor, whose clinical trials are currently suspended, on diabetic complications. Additionally, we found that PKC-alpha pathway, which is not activated by high glucose stimulation, also strongly activates MR. This result is consistent with the clinical fact that PKC-beta inhibitor alone does not completely prevent the development of diabetic complications. Our findings indicate that double blockade of PKC-alpha and beta may be necessary for prevention of diabetic complications.
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