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Experimental diabetic renal growth: role of growth hormone and insulin-like growth factor-I
Authors:Muchaneta-Kubara, E. C.   Sayed-Ahmed, N.   Besbas, N.   Zhang, G.   Cope, G. H.   El Nahas, A. M.
Affiliation:1Sheffield Kidney Institute, Northern General Hospital Sheffield, UK 2Department of Biomedical Science, University of Sheffield Sheffield, UK
Abstract:We have compared the kidneys of two inbred strains of rats (Lewisand Lewis-Dwarf) 7 days after the induction of diabetes mellituswith streptozotocin, in order to examine the influence of aselective growth hormone (GH) deficiency on diabetic renal growthand insulin-like growth factor-I (IGF-I) content of the kidneys.Insulin-like growth factor-I was measured by radioimmunoassayand its distribution within the kidney by immunohistochemicalstaining. We detected a significant increase in both the wetweight (32.9±5.3%, P=0.0085) and dry weight (16.3±6.3%,P=0.046) of the kidneys of diabetic Lewis rats but dwarf rats,selectively deficient in GH, did not show a significant increasein either parameter. Extractable IGF-I increased within thekidneys of diabetic rats of both strains but to a lesser extentin the dwarf rats (+105±28% and +65±21% respectively,P<0.0l). In diabetic Lewis rats a positive correlation wasnoted between the severity of glycaemia and kidney IGF-I content(r=0.604, P<0.05) but no such correlation was noted in dwarfrats. Insulin-like growth factor-I immunostaining increased in diabeticrats of both strains, mainly within cells of the thick ascendinglimb of the loop of Henle including damaged and vacuolated cells.However, morphometric analysis of the staining showed that itwas significantly less widespread in the diabetic dwarf rats(P=0.026). We conclude that growth hormone deficiency bluntsexperimental diabetic renal growth and restricts the increasein the kidney IGF-I content. These findings raise further questionsconcerning the contribution of GH and IGF-I to the early stagesof experimental diabetic renal disease.
Keywords:insulin-like growth factor I   growth hormone   streptozotocin-induced diabetes mellitus   diabetic renal growth
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