Protection against Diabetes-Induced Nephropathy in Growth Hormone Receptor/Binding Protein Gene-Disrupted Mice1.

To further investigate the role of GH in diabetic nephropathy, experimental diabetes was induced with streptozotocin (STZ) in mice in which the GH receptor/binding protein gene was disrupted. Body weight, blood glucose, and renal histology and morphometry were studied 10 weeks after diabetes induction in wild-type (+/+) mice and in mice heterozygous (+/−) and homozygous (−/−) for the disruption. Equivalent levels of hyperglycemia developed in all diabetic groups. Normal weight gain was absent in +/+ and +/− diabetic groups, and− /− diabetics lost weight during the study. Diabetic +/+ and +/− groups both showed evidence of glomerulosclerosis, increases in glomerular volume, and increases in the ratio of mesangial area to total glomerular area, whereas diabetic −/− mice showed none of these pathological changes. These results extend our previous findings of protection against diabetes-associated kidney damage in transgenic mice expressing a GH antagonist. Taken together, the results argue for an important r...

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