| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Diabetic cardiomyopathy (DMCM) is characterized by the left ventricular (LV) diastolic dysfunction in the early stage. We aimed to clarify the underlying mechanism of Ca2+ signaling defects in the early DMCM. In the diabetes mellitus model mice 4 weeks after intraperitoneal streptozotocin injection (STZ-4W), diastolic function was impaired without systolic dysfunction. In the ventricle of STZ-4W mice, the phosphorylation levels of phospholamban (p-PLN) and eNOS (p-eNOS) were significantly lower than that of control mice. The chronic insulin administration restored the ventricular p-PLN and p-eNOS levels and diastolic function in vivo. We further found that insulin/NO/PKG signaling is involved in maintaining the basal level of phosphorylated PLN. These effects were not correlated with blood glucose level. These results indicate that the reduction of p-PLN level caused by loss of insulin signaling is crucial for LV diastolic dysfunction in the early onset of DMCM.
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