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

Edison Biotechnology Institute (L.L.B., A.N.H., J.J.K.) and the Department of Biomedical Sciences (J.J.K.), College of Osteopathic Medicine, Ohio University; Athens, Ohio 45701; and the Division of Nephrology, Department of Medicine, University of Miami School of Medicine (S.D., L.J.S., G.E.S.), Miami, Florida 33136

Address all correspondence and requests for reprints to: Dr. John J. Kopchick, Edison Biotechnology Institute, Konneker Research Laboratory, The Ridges, Ohio University, Athens, Ohio 45701. E-mail: kopchick{at}ohio.edu

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 role of GH in the development of diabetes induced end-organ damage.

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