Protection against diabetes-induced nephropathy in growth hormone receptor/binding protein gene-disrupted mice

To further investigate the role of GH in diabetic nephropathy, experimental diabetes was induced with streptozotocin (STZ) in mice in which the GH rec eptor/binding protein gene was disrupted. Body weight, blood glucose, and r enal histology and morphometry were studied 10 weeks after diabetes inducti on 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 gro ups, and -/- diabetics lost weight during the study. Diabetic +/+ and +/- g roups both showed evidence of glomerulosclerosis, increases in glomerular v olume, and increases in the ratio of mesangial area to total glomerular are a, whereas diabetic -/- mice showed none of these pathological changes. The se results extend our previous findings of protection against diabetes-asso ciated kidney damage in transgenic mice expressing a GH antagonist. Taken t ogether, the results argue for an important role of GH in the development o f diabetes induced end-organ damage.