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

• Published in: Endocrinology (Philadelphia) 2000-01, Vol.141 (1), p.163-168
• Main Authors: Bellush, Linda L, Doublier, Sophie, Holland, Amy N, Striker, Liliane J, Striker, Gary E, Kopchick, John J
• Format: Article
• Language: English
• Subjects: Body weight; Damage; Diabetes; Diabetes mellitus; Growth hormones; Histology; Hyperglycemia; Morphometry; Nephropathy; Proteins; Receptors; Streptozocin; Transgenic mice; Weight
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.141.1.7284

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.