This study was performed to evaluate the composition of the extracellular matrix of the mesangium in both diabetic and nondiabetic rats. Four groups of rats (n = 10 each) were studied. Nondiabetic rats were injected with saline (group 1) or insulin (3.5 U NPH daily) (group 2). Streptozocin-induced diabetic rats were similarly injected with saline (group 3) or insulin (group 4). Six weeks after initiation of study, glomerular diameter (µm) was increased in groups 2 (147 ± 21), 3 (144 ± 22), and 4 (150 ± 7) compared with group 1 (104 ± 12) (P < .01). Glomerular hypertrophy was associated with an increase in the relative amount of mesangial matrix as determined by staining for fibronectin. By immunofluorescence microscopy (0–4+ scale), type I collagen antigen was not detected in the mesangium of any of the experimental groups. Staining for type V collagen and thrombospondin was similar between the experimental groups. Type III collagen antigen was not detected in the mesangium of control (group 1) or insulin-deficient diabetic rats (group 3); however, it was detected (2–3+) in the mesangium of both insulin-treated diabetic and nondiabetic rats (Mann-Whitney, P < .01). Comparable intensity of staining (1+) for type IV collagen antigen was detected in the mesangium of animals from groups 1, 2, and 4; however, the staining intensity was markedly increased (3+) in insulindeficient diabetic rats (group 3; Mann-Whitney, P < .01). These studies demonstrate that glomerular hypertrophy and an increase in mesangial matrix occur in both hyperglycemic and insulin-treated rats; however, the mesangial matrix composition varies with the metabolic environment. Hyperglycemia is associated with a significant increase in the content of type IV collagen, and insulin treatment is associated with a switch in the matrix composition with the new expression of type III collagen. The significance of these findings in the evolution of diabetic glomerulosclerosis is discussed.

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