| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Outline of Final Research Achievements |
SDF-1alpha is an important substrate of DPP-4. We investigated the role of SDF-1alpha in the pathogenesis of diabetic nephropathy and its modification by DPP-4 inhibition independent of GLP-1 receptor signaling using nephropathy-prone KK/Ta-Akita diabetic mice. Increased SDF-1 expression was observed in glomerular podocytes and distal nephrons. DPP-4 inhibitor linagliptin, but not GLP-1 receptor agonist liraglutide, further augmented renal SDF-1 expression. The progression of albuminuria, glomerulosclerosis, periglomerular fibrosis, and renal oxidative stress was suppressed by linagliptin treatment. Linagliptin treatment increased urinary sodium excretion and attenuated the increase in GFR which reflects glomerular hypertension. We conclude that DPP-4 inhibition, independent of GLP-1 receptor signaling, contributes to protection of the diabetic kidney through SDF-1-dependent antioxidative effects and amelioration of adverse renal hemodynamics.
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