Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats |
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| Authors: | Li Wei Zhu Li-hua Wang En-bi Ye Zeng-can Lin Jun Guo Li-he Luo Fei-hong Liu Xi-hong Fang Xin Shen Shui-xiang |
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| Affiliation: | Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 200031, China. |
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| Abstract: | AIM: To explore the feasibility of human growth hormone (hGH) receptor antagonist in the treatment of end-stage diabetic renal complications. METHODS: Two hGH mutants, hGHA1 (Cys-hGH-del1-4, G120R, K168A, E174A, C182S, del186-191) and hGHA2 (hGH-H21A, G120R, E174A) were expressed in E coli. The IC50 (Mean+/-SD) values for the mutants for inhibiting 125I-hGH binding to rabbit growth hormone receptor were (65+/-10) ng for hGHA1, (27+/-5.6) ng for hGHA2, and (10+/-0.6) ng for wild type hGH, respectively. RESULTS: After treatment for 12 weeks, the renal histology analysis showed that treatment with hGHA2 at 4 mg/kg body weight daily markedly suppressed glomerulosclerosis in streptozotocin-induced diabetic Sprague-Dawley (SD) rats; hGHA1 at the same dosage slightly increased the renal damage compared with saline; while wild type hGH at 1 U/kg body weight daily severely worsened the glomerulo-sclerosis in diabetic SD rats. CONCLUSION: The data indicated that hGHA2 inhibited the end-stage glomerulosclerosis in diabetic rats, but hGHA1 mildly increased the glomerulosclerosis. |
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| Keywords: | growth hormone diabetic nephropathies mutation diabetes mellitus |
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