No abstract

It appears that KK-A(y)/Ta mice, especially in terms of histopathological findings, are a suitable animal model for the early stage of type 2 diabetic nephropathy.

To determine correlations among the levels of urinary MMP-9 and type-IV collagen, hyperglycemia, urinary protein excretion, and renal injuries in patients with type 2 diabetic nephropathy, we measured levels of urinary MMP-9 and protein, blood urea nitrogen (BUN), serum creatinine (s-Cr), fasting plasma glucose (FPG), and glycohemoglobin A1c (HbA1c) in 47 diabetic patients and 14 healthy adults. Urinary type-IV collagen was also measured in 28 diabetic patients and seven healthy adults. Patients with diabetic nephropathy were divided into two groups: 1). patients with normoalbuminuria or microalbuminuria (0-299 mg/g.Cr; n=27), and 2). patients with macroalbuminuria (>300 mg/g.Cr; n=20). The mean level of urinary MMP-9 in group 2 was significantly higher than those in healthy adults (P<0.05), and the levels of urinary MMP-9 in patients with diabetic nephropathy increased in accordance with the clinical stage of the disease. The levels of urinary MMP-9 tended to be correlated with HbA1c in these patients, but the correlation was not statistically significant. The mean level of urinary type-IV collagen in group 2 of patients with diabetic nephropathy was significantly higher than that in group 1 and healthy adults. Levels of urinary type-IV collagen in patients with diabetic nephropathy also increased in accordance with the clinical stage of the disease. The results suggest that measurements of urinary MMP-9, as well as urinary type-IV collagen, may be useful for evaluating the degree of renal injuries in patients with type 2 diabetic nephropathy, especially in the early stage.

No abstract

No abstract

Podocyte loss was well known in type 2 diabetic nephropathy patients. The objective of the present study was to determine the number of podocytes and the degree of albuminuria in diabetic KK-A y /Ta (KK-A y ) mice which had been reported as diabetic nephropathy model. Diabetic KK-A y mice, diabetic KK/Ta mice and nondiabetic BALB/cA Jcl (BALB/cA) mice were studied. We analyzed glomerular lesions in all mice by morphometric analysis and immunofluorescence to determine the number of podocytes. Level of urinary albumin was also measured. Glomerular enlargement and mesangial expansion were observed in KK-A y mice. Mean number of podocytes per glomerulus (NG pod) in diabetic KK-A y mice was significantly lower than that in non-diabetic BALB/cA mice. Mean NG pod/glomerular area (GA) per glomerulus was also significantly decreased in diabetic KK-A y mice. The level of urinary albumin/creatinine ratio (ACR) in diabetic KK-A y mice was significantly higher than that in non-diabetic BALB/cA mice. These data suggest that podocyte loss might induce albuminuria in KK-A y mice. This finding confirmed our previous report that KK-A y mice, especially in terms of histological findings, are a suitable animal model for glomerular injury in type 2 diabetic nephropathy.