RGD Reference Report - Growth hormone receptor antagonism prevents early renal changes in nonobese diabetic mice. - Rat Genome Database

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

Authors: Segev, Y  Landau, D  Rasch, R  Flyvbjerg, A  Phillip, M 
Citation: Segev Y, etal., J Am Soc Nephrol. 1999 Nov;10(11):2374-81.
RGD ID: 2307370
Pubmed: PMID:10541297   (View Abstract at PubMed)

The growth hormone (GH)/insulin-like growth factor (IGF) axis is involved in diabetic renal disease. The role of a specific GH receptor (GHR) antagonist in the development of early renal changes in nonobese diabetic (NOD) mice was investigated. Female diabetic (nonketotic) NOD mice treated with a polyethylene glycol-treated GHR antagonist (2 mg/kg, every other day) (DA group) or saline (D group) and their nonhyperglycemic age-matched littermates (control animals) were euthanized 3 wk after the onset of diabetes. Body weights at euthanasia were similar among the groups. Serum GH levels were markedly elevated, and serum IGF-I levels were significantly decreased in D and DA animals, compared with controls. The increases in kidney weights and glomerular volumes observed for the D group were absent in the DA group. Albuminuria was increased in the D group but was normalized in the DA group. Extractable renal IGF-I protein levels were increased in the D group but were partially normalized in the DA group. Renal IGF-binding protein 1 mRNA levels were increased in the D group but returned to almost normal levels in the DA animals. Kidney IGF-I and GHR mRNA levels were decreased in both the D and DA groups. Renal GH-binding protein mRNA levels remained unchanged in both diabetic groups. GHR antagonism had a blunting effect on renal/glomerular hypertrophy and albuminuria in diabetic NOD mice. These salutary effects were associated with concomitant inhibition of increased renal IGF-I protein levels and were obtained without affecting either somatic growth or circulating GH and IGF-I levels. Therefore, modulation of GH effects may have beneficial therapeutic implications in diabetic nephropathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diabetic Nephropathies  ISOGhr (Mus musculus)2307370; 2307370associated with Diabetes MellitusRGD 
Diabetic Nephropathies  IMP 2307370associated with Diabetes MellitusRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ghr  (growth hormone receptor)

Genes (Mus musculus)
Ghr  (growth hormone receptor)

Genes (Homo sapiens)
GHR  (growth hormone receptor)


Additional Information