Comparison between somatostatin analogues and ACE inhibitor in the NOD mouse model of diabetic kidney disease

Segev, Yael; Eshet, Renanah; Rivkis, Inessa; Hayat, Chen; Kachko, Leonid; Phillip, Moshe; Landau, Daniel

doi:10.1093/ndt/gfh528

Cited by 13 publications

(12 citation statements)

References 15 publications

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“…GH replacement in men with abdominal obesity can diminish the negative metabolic consequences of visceral obesity [22], suggesting that low levels of this hormone are important for the metabolic aberrations in obese type 2 diabetic patients [23]. In our study we showed that the addition of a GH antagonist (somatostatin) did not affect any of the renal parameters (hypertrophy, hyperfiltration and albuminuria), contrary to previous reports on beneficiary effects of GH antagonists in type 1 diabetes mellitus [13], thus supporting the concept that no further suppression of GH is indicated in type 2 diabetes mellitus.…”

Section: Discussioncontrasting

confidence: 99%

“…Immunoassays for serum GH Serum GH was measured by RIA, as previously described [13], using a specific polyclonal antibody. The sensitivity of the method was 0.04 ng murine GH per tube; the CVs for tested sera at 13.9 and 201.1 μg/l were 13.6 and 5.9%, respectively.…”

Section: Animal Experimentationmentioning

confidence: 99%

“…Immunoassays for serum IGF1 Serum IGF1 was measured as previously described [13], by the functional separation method, in which excess IGF2 blocks the interference of IGF binding proteins. The test sensitivity was 0.02 ng IGF1 per tube; the intra-assay CVs for sera with IGF1 levels ranging between 80, 212 and 412 ng/ml were 8.9, 2.9 and 9.6%, respectively.…”

Section: Animal Experimentationmentioning

confidence: 99%

“…A modified ELISA determined the urinary albumin concentration in the urine samples as previously described [13]. Intra-and inter-assay CVs were less than 5 and 10%, respectively.…”

Section: Animal Experimentationmentioning

confidence: 99%

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

et al. 2007

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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.

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Section: Discussioncontrasting

confidence: 99%

Section: Animal Experimentationmentioning

confidence: 99%

Section: Animal Experimentationmentioning

confidence: 99%

“…A modified ELISA determined the urinary albumin concentration in the urine samples as previously described [13]. Intra-and inter-assay CVs were less than 5 and 10%, respectively.…”

Section: Animal Experimentationmentioning

confidence: 99%

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

et al. 2007

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“…[4][5][6]12] Increased circulating growth hormone levels have been reported in rodents with diabetic nephropathy. [13] In some experimental studies, growth hormone receptor antagonist's treatment protected the animals against development of renal changes. [14,15] Although it is well known that ghrelin is a growth hormone secretagogue, there have been no studies that investigate the relationship between increased ghrelin and growth hormone in diabetic nephropathy.…”

Section: Discussionmentioning

confidence: 99%

Determination of Ghrelin Immunoreactivity in Kidney Tissues of Diabetic Rats

Kuloğlu

Dabak

2009

Renal Failure

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Backgrounds/Aims. Ghrelin, a recently discovered hormone, is released largely from stomach and might affect insulin secretion and glucose metabolism. The aim of this study was to determine the immunohistochemical localization of ghrelin in streptozotocin-induced diabetic rat kidneys. Methods. Fifty-four adult male Wistar rats were used in this study. All rats were divided into nine groups according to three time points of the study (2, 4, and 6 weeks) as control group, control group given 0.1 M phosphatecitrate, and diabetic group given 50 mg/kg streptozotocin intraperitoneally. The rats in all groups were decapitated at the end of 2, 4, and 6 weeks of the study. The kidneys of the rats were removed, and tissue samples were processed by using routine paraffin techniques. The samples were immunohistochemically stained using avidin-biotin-peroxidase method for ghrelin immunoreactivity. Results. There were no differences of ghrelin immunoreactivity between the control groups. Ghrelin immunoreactivity was observed in both distal tubulus and collecting ducts in the diabetic groups, while it was detected only in distal tubules of the control groups. The intensity of ghrelin immunoreactivity was increased at 4 and 6 weeks of the study in the diabetic groups. Conclusion. Increased ghrelin immunoreactivity in the diabetic rat kidney tissues suggests that ghrelin may contribute to the pathophysiological mechanism of diabetic nephropathy.

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Novel roles of the IGF–IGFBP axis in etiopathophysiology of diabetic nephropathy

Vasylyeva

Ferry

2007

Diabetes Research and Clinical Practice

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Mechanisms contributing to development of diabetic nephropathy (DN) remain unclear. High ambient glucose level transforms intracellular pathways, promoting stable phenotypic changes in the glomerulus such as mesangial cell hypertrophy, podocyte apoptosis, and matrix expansion. Insulin-like growth factors (IGFs) and the high affinity IGF binding proteins (IGFBPs) exert major effects on cell growth and metabolism. Compared with diabetic patients without microalbuminuria (MA), MA diabetic patients display perturbed GH-IGF-IGFBP homeostasis, including increased circulating IGF-I and IGFBP-3 protease activity, increased excretion of bioactive GH, IGF-I, and IGFBP-3, but decreased circulating IGFBP-3 levels. In diabetic animal models, expression of IGF-I and IGFBP-1 to -4 increases in key renal tissues and glomerular ulrafiltrate. Epithelial, mesangial, and endothelial cells derived from the kidney respond to IGF-I binding with increased protein synthesis, migration, and proliferation. This article reviews classic and emerging concepts for the roles of the GH-IGF-IGFBP axis in the etiopathophysiology, treatment, and prevention of diabetic renal disease. We report IGF-independent actions of IGFBP-3 in the podocyte for the first time.

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Comparison between somatostatin analogues and ACE inhibitor in the NOD mouse model of diabetic kidney disease

Cited by 13 publications

References 15 publications

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

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

Determination of Ghrelin Immunoreactivity in Kidney Tissues of Diabetic Rats

Novel roles of the IGF–IGFBP axis in etiopathophysiology of diabetic nephropathy

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