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Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats

Wei Li1, Li-hua Zhu, En-bi Wang

  • 1Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 200031, China.

Acta Pharmacologica Sinica
|April 7, 2004
PubMed
Abstract

Insights

Human growth hormone (hGH) receptor antagonists show potential for treating diabetic kidney disease. One mutant, hGHA2, suppressed glomerulosclerosis in diabetic rats, while hGHA1 worsened it.

Area of Science:

  • Endocrinology
  • Nephrology
  • Biochemistry

Background:

  • Diabetic renal complications, including glomerulosclerosis, represent a significant challenge in diabetes management.
  • Human growth hormone (hGH) plays a role in metabolic processes, and its dysregulation can contribute to diabetic nephropathy.

Purpose of the Study:

  • To investigate the therapeutic potential of novel human growth hormone (hGH) receptor antagonists in mitigating end-stage diabetic renal complications.
  • To evaluate the efficacy of two specific hGH mutants, hGHA1 and hGHA2, in a preclinical model of diabetic nephropathy.

Main Methods:

  • Two hGH receptor antagonist mutants, hGHA1 and hGHA2, were engineered and expressed in E. coli.
  • The inhibitory activity of these mutants on 125I-hGH binding to the growth hormone receptor was determined by IC50 values.
  • The in vivo efficacy was assessed in streptozotocin-induced diabetic Sprague-Dawley rats over a 12-week treatment period.

Main Results:

  • hGHA2 treatment (4 mg/kg daily) significantly suppressed glomerulosclerosis in diabetic rats.
  • hGHA1 treatment (4 mg/kg daily) showed a slight increase in renal damage compared to saline control.
  • Wild-type hGH treatment (1 U/kg daily) severely exacerbated glomerulosclerosis in the diabetic rat model.

Conclusions:

  • The hGH receptor antagonist hGHA2 demonstrates a protective effect against glomerulosclerosis in diabetic nephropathy.
  • hGHA1 exhibited a contrasting effect, potentially worsening renal damage, highlighting the importance of specific mutant design.
  • These findings suggest that targeted inhibition of the hGH receptor pathway holds promise for managing advanced diabetic kidney disease.

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