Growth hormone receptor antagonism prevents early renal changes in nonobese diabetic mice

The growth hormone (GH)/insulin-like growth factor (ICF) axis is involved i n diabetic renal disease. The role of a specific GH receptor (GHR) antagoni st in the development of early renal changes in nonobese diabetic (NOD) mic e was investigated. Female diabetic (nonketotic) NOD mice treated with a po lyethylene glycol-treated GHR antagonist (2 mg/kg, every other day) (DA gro up) or saline (D group) and their nonhyperglycemic age-matched littermates (control animals) were euthanized 3 wk after the onset of diabetes. Body we ights at euthanasia were similar among the groups. Serum GH levels were mar kedly elevated, and serum IGF-I levels were significantly decreased in D an d DA animals, compared with controls. The increases in kidney weights and g lomerular volumes observed for the D group were absent in the DA group. Alb uminuria was increased in the D group but was normalized in the DA group. E xtractable renal IGF-I protein levels were increased in the D group but wer e partially normalized in the DA group. Renal IGF-binding protein 1 mRNA le vels were increased in the D group but returned to almost normal levels in the DA animals. Kidney ICF-I and GHR mRNA levels were decreased in both the D and DA groups. Renal OH-binding protein mRNA levels remained unchanged i n both diabetic groups. GHR antagonism had a blunting effect on renal/glome rular hypertrophy and albuminuria in diabetic NOD mice. These salutary effe cts were associated with concomitant inhibition of increased renal IGF-I pr otein levels and were obtained without affecting either somatic growth or c irculating GH and IGF-I levels. Therefore, modulation of GH effects may hav e. beneficial therapeutic implications in diabetic nephropathy.