Effects of Graded Control of Blood Glucose with Insulin on the Progression of Experimental Diabetic Nephropathy / 대한신장학회잡지

ABSTRACT

Intensive insulin therapy effectively delays the onset and slows the progression of nephropathy in patients with IDDM. TGF- 0 has recently been implicated in the pathogenesis of diabetic nephropathy. We evaluated the effects of different level of glucose control with insulin therapy on the progression of diabetic nephropathy in age-matched control rats(C) and 3 groups of streptozotocininduced diabetic rats', high blood glucose diabetic rats without insulin therapy(HG), rnoderate glucose diabetic rats with insulin therapy(MG), and normal glucose diabetic rats with intensive insulin treatment (NG). Glomerular volume(VG) was measured using Image-Pro morphometric software, glomerular TGF- Bl mRNA expression by in situ hybridization, and glomerular expression of TGF-8 and type IV collagen proteins by immunohistochemical staining. VG was significantly higher in HG than in other groups in 12 weeks. Kidney weight(KW) was the highest while the body weight the lowest in HG of all groups in 12 weeks. Daily urine albumin excretion (UAE) increased with time in all groups but was significantly larger in HG than in all other groups in 12 weeks. MG also had significantly larger UAE than C in 12 weeks. There was no difference in VG, KW, and UAE between NG and C. Glomerular TGF-Bl mRNA expression was significantly higher in HG than in all the rest of the groups in 4 and 12 weeks. Glomerular expression of TGF-B and type IV collagen proteins was proportional to the levels of blood glucose, being the highest in HG in 12 weeks. There was little or no expression of TGF-0 1 mRNA and protein or type IV collagen protein in NG. Thus these results support the view that high blood glucose is the prerequisite for glomerular injury in diabetes mellitus and that the glomerular injury in diabetes mellitus is mediated, in part, by TGF-01 and suppressed by glucose control.