Reversal of Glomerular Hyperfiltration and Renal Hypertrophy by Blood Glucose Normalization in Diabetic Rats

Abstract

Two groups of rats with streptozocin-induced diabetes and one group of nondiabetic control rats were studied. Group 1 diabetic rats received daily insulin to maintain blood glucose levels at 300–400 mg/dl for 44 wk. Group 2 diabetic rats received the same insulin regimen for 37 wk and then received an increased dose of insulin to return blood glucose levels close to normal for 7 wk. Group 3 nondiabetic rats were age-matched controls. Glomerular filtration rate (GFR) and kidney weight were elevated in moderately hyperglycemic group 1 rats compared with group 3 rats. Normalization of blood glucose returned both GFR (group 1,1.83 ± 0.04 ml/min; group 2,1.36 ± 0.05 ml/min; group 3,1.45 ± 0.07 ml/min) and kidney weight (group 1, 2.55 ± 0.06 g; group 2,1.82 ± 0.05 g; group 3,1.72 ± 0.06 g) to normal in group 2 rats. Despite a sustained increase in GFR, group 1 rats did not exhibit any increase in glomerular volume (group 1, 2.77 ± 0.09 × 106 μm3; group 2, 2.69 ± 0.09 × 106 μm3; group 3, 2.81 ± 0.7 × 106 μm3). Group 1 rats did, however, exhibit a significant increase in glomerular mesangial volume (group 1, 0.31 ± 0.02 × 106 μm3; group 2, 0.28 ± 0.02 × 106 μm3; group 3, 0.21 ± 0.01 × 106 μm3), which was not reversed by normalization of blood glucose in group 2. These findings show that normalization of blood glucose can reverse established glomerular hyperfiltration and renal hypertrophy in moderately hyperglycemic diabetic rats. They further indicate that mesangial expansion is associated with sustained moderate hyperglycemia in this disease model.