The effect of growth hormone on the development of diabetic kidney disease in rats

Landau, Daniel; Israel, Eytan; Rivkis, Inessa; Kachko, Leonid; Schrijvers, Bieke F.; Flyvbjerg, Allan; Phillip, Moshe; Segev, Yael

doi:10.1093/ndt/gfg142

Cited by 30 publications

(21 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Liver IGF-I, GHR, and IGF binding protein-1 (IGFBP-1) mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR) method as previously described (18). PCR products were quantified densitometrically using Fluorchem software (Alpha-Innotech, San Leandro, CA).…”

Section: Mrna Studies and Western Immunoblot Analysismentioning

confidence: 99%

Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats

Tarasiuk¹,

Segev²

2007

Journal of Applied Physiology

View full text Add to dashboard Cite

Tarasiuk A, Segev Y. Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats. J Appl Physiol 102: [913][914][915][916][917][918] 2007. First published November 30, 2006; doi:10.1152/japplphysiol.00838.2006.-The effect of upper airway loading on longitudinal bone growth and various components of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis has not been fully elucidated. In the present study, the effect of chronic resistive airway loading (CAL) in a prepubescent rat model on linear bone growth and weight gain was investigated. We hypothesize that CAL induced in prepubescent rats will lead to impaired longitudinal growth due to impairment in circulating and liver GH/IGF-I parameters. The tracheae of 22-day-old rats were obstructed by tracheal banding to increase inspiratory esophageal pressure. The GH/IGF-I markers were analyzed using ELISA, RT-PCR, and Western immunoblot analysis 14 days after surgery. Animals exhibited impaired longitudinal growth as demonstrated by reduction of tibia and tail length gains by 40% (P Ͻ 0.0001) and body weight gain by 24% (P Ͻ 0.0001). No differences were seen in total body energy balance, i.e., oxygen consumption, daily food intake, or arterial blood gases. Circulating GH, IGF-I, and IGF binding protein-3 (IGFBP-3) levels were reduced by 40% (P ϭ 0.037), 30% (P Ͻ 0.006), and 27% (P ϭ 0.02), respectively, in the CAL group. Liver IGF-I mRNA level decreased by 20% (P Ͻ 0.0002), whereas GH receptor mRNA and protein expression were unchanged. We conclude that impaired longitudinal growth in prepubescent CAL rats is related to a decrease in GH, IGF-I, and IGFBP-3 levels. chronic resistive loading; growth hormone; insulin-like growth factor I; insulin-like growth factor binding protein-3; prepuberty ONE OF THE CONSEQUENCES OF chronic resistive airway loading (CAL) in adult rats is malfunction in body weight gain (12, 27) without effect on longitudinal bone growth (35). The failure to gain weight was not related to decreased caloric intake (12) and was recently attributed to a decline in serum insulin-like growth factor I (IGF-I) levels (35). The endocrine effect of pituitary-secreted growth hormone (GH) is induction of IGF-I and IGF binding protein-3 (IGFBP-3) synthesis in various organs, including the liver; both are highly correlated with the 24-h mean GH levels (3, 7). This effect is mediated via activation of GH receptor (GHR), which is extensively distributed throughout many tissues (9). Impairment of the GH/IGF-I axis in prepubescent rats, before bone growth is completed, leads to skeletal growth retardation (31). The effect of CAL on the GH/IGF-I axis and longitudinal growth in prepuberty rats is not known.In the present study, the effect of CAL on longitudinal growth and weight gain was studied using the prepubescent rat model. We hypothesize that CAL will impair the GH/IGF-I axis, consequently leading to longitudinal growth retardation. We explored the effect of CAL on linear growth, serum GH, IGF-I, and ...

show abstract

Section: Mrna Studies and Western Immunoblot Analysismentioning

confidence: 99%

Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats

Tarasiuk¹,

Segev²

2007

Journal of Applied Physiology

View full text Add to dashboard Cite

show abstract

“…mRNA studies Total RNA was prepared from frozen tissues by the standard methods. Evaluation of renal and liver Igf1 and Igfbp1 mRNAs was performed using the RT-PCR method, as previously described [10].…”

Section: Estimation Of Glomerular Volumementioning

confidence: 99%

“…Western immunoblot analysis Western immunoblot analysis was performed from kidney and liver samples as previously described [10]. For the detection of kidney phosphorylated forkhead box O1 (FOXO1) (Ser256) and liver GHR, 200-μg portions of sample protein were loaded in each gel lane, subjected to 10% SDS polyacrylamide gel and electroblotted into nitrocellulose membranes.…”

Section: Estimation Of Glomerular Volumementioning

confidence: 99%

“…Subsequently, we have shown that a GHR antagonist had salutary effects on DN markers, in association with a concomitant inhibition of renal IGF1 protein accumulation, but without affecting either somatic growth or circulating GH and IGF1 levels [9]. In contrast, administration of GH to streptozotocin-induced diabetic rats exacerbated DN in association with a marked increase in renal IGFBP1 message [10], adding another aspect to the pathogenic role of GH in DN. Thus, inhibition of GH action may have therapeutic implications for type 1 diabetic patients with DN.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Systemic and renal growth hormone–IGF1 axis involvement in a mouse model of type 2 diabetes

et al. 2007

Self Cite

View full text Add to dashboard Cite

Aims/hypothesis In previous studies we have shown a significant involvement of the growth hormone (GH)-IGF axis in animal models of type 1 diabetes mellitus, but the role of this endocrine system in type 2 diabetes mellitus is less well characterised. We therefore examined the endocrine and renal GH-IGF axis changes in db/db mice, a model of type 2 diabetes mellitus and nephropathy. Materials and methods Obese and lean animals were followed, beginning at hyperglycaemia onset, for 4 weeks. Albuminuria and creatinine clearance, as well as kidney and glomerular morphology were assessed. Tissue protein levels were determined by western blotting and mRNA levels by RT-PCR.Results Serum GH and IGF1 levels immediately prior to killing were decreased and liver mRNA levels of insulinlike growth factor binding protein 1 (Igfbp1) were increased in obese animals. Kidney weight was increased in obese animals, associated with hyperfiltration, albuminuria and glomerular hypertrophy. Administration of a somatostatin analogue (PTR-313) did not improve any of these parameters of diabetic renal involvement. Renal Igf1 mRNA was decreased and renal Igfbp1 mRNA and protein were significantly increased in obese animals. Renal insulindriven levels of phosphorylated forkhead box O1 (FOXO1) were decreased in obese animals. Conclusions/interpretation Diabetic db/db mice show significant renal changes (and IGFBP1 renal accumulation), similar to the findings in models of type 1 diabetes mellitus. A decreased signalling through the insulin receptor and decreased FOXO1 phosphorylation may allow Igfbp1 gene transcription. These renal changes are associated with low circulating IGF1 and GH levels and unchanged hepatic growth hormone receptor expression, unlike the condition in type 1 diabetes mellitus. This suggests that further GH inhibition to modulate renal complications in type 2 diabetes mellitus is not indicated.

show abstract

“…A deleterious effect of GH on the rodent kidney has been noted by several investigators. 44,45 Fortunately, this noxious effect seems to be limited to rodents, because prolonged treatment of children with uremia has not been associated with adverse renal effects. 46 Because of its physiologic role in regulating cardiac structure and function, there has been interest in evaluating whether GH might be beneficial in cardiac disease treatment.…”

Section: Tgf-␤ Immunostaining Was Markedly Increased In Crf Heart (Crmentioning

confidence: 99%

Low-Dose Growth Hormone is Cardioprotective in Uremia

Rabkin

Awwad

Chen

et al. 2008

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Growth hormone (GH) is required to maintain normal cardiac structure and function and has a positive effect on cardiac remodeling in experimental and possibly human disease. Cardiac resistance to GH develops in the uremic state, perhaps predisposing to the characteristic cardiomyopathy associated with uremia. It was hypothesized that administration of low-dosage GH may have a salutary effect on the cardiac remodeling process in uremia, but because high levels of GH have adverse cardiac effects, administration of high-dosage GH may worsen uremic cardiomyopathy. In rats with chronic renal failure, quantitative cardiac morphology revealed a decrease in total capillary length and capillary length density and an increase in mean intercapillary distance and fibroblast volume density evident. Low-dosage GH prevented these changes. Collagen and TGF-␤ immunostaining, increased in chronic renal failure, were also reduced by GH, suggesting a mechanism for its salutary action. Low-dosage GH also prevented thickening of the carotid artery but did not affect aortic pathology. In contrast, high-dosage GH worsened several of these variables. These results suggest that low-dosage GH may benefit the heart and possibly the carotid arteries in chronic renal failure.

show abstract

The effect of growth hormone on the development of diabetic kidney disease in rats

Cited by 30 publications

References 19 publications

Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats

Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats

Systemic and renal growth hormone–IGF1 axis involvement in a mouse model of type 2 diabetes

Low-Dose Growth Hormone is Cardioprotective in Uremia

Contact Info

Product

Resources

About