| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Since a sizable number of diabetic patients enter regular dialysis, elucidation of the mechanism whereby diabetic nephropathy progresses is of immediate importance Adiponectin (ADPN), a 30 kDa protein exclusively secreted by adipocytes, acts as an anti-diabetic and anti-atherogenic hormone It has recently been reported that plasma concentration of ADPN is reduced in diabetes in both humans and experimental animals. However, the pathophysiological significance of ADPN is largely unknown. Thus, we have investigated a role of ADPN in the pathogenesis of diabetic nephropathy. Mild diabetes was induced in 7 week-old rats by a single i. v. injection of streptozotocin (40 mg/kg). The rats remained non-ketotic without insulin throughout the experimental period of 24 weeks. Vehicle-injected rats were used as control. At 8, 16 and 24 weeks after the injection of streptozotocin, blood and urine samples were collected, and rats were sacrificed. In diabetic rats, fasting blood glucose, total choles
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terol and triglyceride increased several folds from the values in control rats during 4 to 24 weeks. HbAlc also increased from <2.5% to 8.2%. Beyond 12 weeks, urinary protein excretion increased modestly in diabetic rats from 15 to 45 mg/day. Neither blood pressure nor plasma creatinine changed significantly. ADPN immunostaining in the glomerulus was faint in the control rats, whereas the immunostaining intensified in the diabetic rat with time. Confocal laser scanning mioroscopy revealed that ADPN immunolabeling was confined to endothelial cells and, to a lesser extent, mesangial cells as evidenced by double immunostaining with anti-PECAM (a marker of endothelial cells) or with anti-Thy-1 (a marker ofmesangial cells). Plasma ADPN levels in diabetic rats were reduced to half of those in control rats. These results show that ADPN binds to glomerular endothelial cells and, to a lesser extent, mesangial cells, and this cell-selective binding increases in diabetes, suggesting that ADPN may protect the structure and function of the glomerular capillary in diabetic nephropathy. Less
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