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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indirect data exist which implicate elevated growth hormone (GH) as a factor in the development of diabetic nephropathy. The administration of somatostatin (SRIH) has been shown to reverse many of the changes found in early diabetic nephropathy; however, it is unknown whether SRIH causes these effects by the suppression of GH or by other unspecified factors. To study directly the possible effect of excess GH in the development of diabetic nephropathy, either ovine growth hormone (0.2 mg oGH) or diluent buffer was administered IM daily for 19 weeks to diabetic rats and to controls. Severity of nephropathy was assessed by 24 hour urine albumin excretion (UAE), relative kidney weight, and kidney histology. Results showed that diabetic rats overall had elevated UAE and kidney weight vs non-diabetic rats (46.2 +/- 8.6 vs 5.4 +/- 1.3 mg per day and 5.7 +/- 0.2 vs 2.7 +/- 0.1 mg per g of body weight, respectively, p < 0.001). However, no differences were detected between diabetic rats treated with GH compared to control diabetic rats. Additionally, diabetic rats had histopathologic changes consistent with early diabetic nephropathy, but no difference in severity scores was found between diabetic groups. These data provide evidence against GH as an etiologic factor in the development of diabetic nephropathy and it is speculated by the authors that SRIH exerts its protective renal effects in diabetes by mechanisms other than GH suppression.
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PMID:Effect of chronic growth hormone administration on diabetic nephropathy in the rat. 829 1

Major findings with regard to the somatostatin-growth hormone (GH)-insulin-like growth factor (IGF-1) axis and diabetes are summarized. GH hypersecretion and reduced circulating IGF-1 levels are prevalent in insulin-dependent diabetes. Somatostatin improves metabolism in insulin-dependent diabetics. Insulin resistance and poor metabolic regulation, which may partly be due to hypersecretion of GH, are believed to accelerate the development of diabetic angiopathy. Diabetic hypersomatotrophinemia may be due to hepatic resistance to GH and increased hepatic production of IGF-1-binding protein-1 (IGFBP-1), leading to reduced levels of circulating IGF-1 and further stimulation of GH production. Studies in vitro and in diabetics suggest a causal link between diabetic hypersomatotrophinemia and diabetic angiopathy. In vitro evidence for the involvement of IGF-1 in diabetic angiopathy is reviewed. Also reviewed is evidence, from rat and human studies, of the possible involvement of GH and IGF-1 in diabetic nephropathy. The role of somatostatin in late diabetic vascular complications remains to be elucidated.
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PMID:Somatostatin, growth hormone, insulin-like growth factor-1, and diabetes: friends or foes? 876 94

The aim of this study was to determine the clinical significance of serum and urinary insulin-like growth factor I (IGF-I) in renal disease and diabetes mellitus. In renal portion, we measured their concentrations in patients with chronic renal disease (serum creatinine < 2.0 mg/dl) (CRD. n = 22) and those with chronic renal failure (serum creatinine > or = 2.0 mg/dl) (CRF, n = 26) and compared with normal healthy controls (C. n = 20). Serum concentrations growth hormone (GH) and IGF-I did not differ among these groups. Urinary IGF-I level was significantly increased in CRF (4.0 +/- 0.5 ng/mg creatinine) compared with CRD (2.8 +/- 0.6 ng/mg creatinine) and C (1.8 +/- 1.0 ng/mg) creatinine). Urinary IGF-I did not correlate with either serum GH or serum IGF-I. Urinary IGF-I, but not serum IGF-I, demonstrated a significant negative correlation with creatinine clearance. In diabetic portion, 29 patients with noninsulin dependent diabetes mellitus (NIDDM), whose serum creatinine were within normal range, and age-matched 12 subjects were enrolled. Serum IGF-I in NIDDM (130 +/- 11 ng/ml) was significantly lower than that in controls (201 +/- 11 pg/ml). In contrast, urinary IGF-I level in NIDDM (1.93 +/- 0.31 ng/mg creatinine) did not differ from that in controls (2.00 +/- 0.31 ng/mg creatinine). In NIDDM, urinary IGF-I had poor correlation with both serum IGF-I and albuminuria. The data in renal patients suggest the possible participation of renal IGF-I in the progression of renal disease, while in NIDDM with normal serum creatinine the role of renal IGF-I may be less in the early diabetic nephropathy.
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PMID:Serum and urinary levels of insulin-like growth factor I in patients with chronic renal disease and diabetes mellitus: its clinical implication. 879 28

Transgenic mice expressing growth hormone genes have been shown to have kidney lesions resembling those found in human diabetic patients. However, transgenic mice expressing a growth hormone antagonist gene have normal kidneys. In this study, streptozotocin was used to induce diabetes in growth hormone or growth hormone antagonist transgenic mice and total glycated hemoglobin levels were determined. We found streptozotocin treatment resulted in a significant increase in glycated hemoglobin levels in these animals. Despite comparable levels of glycemia and glycated hemoglobin, severe glomerulosclerosis was found in diabetic and nondiabetic growth hormone transgenic mice; moderate glomerulosclerosis was seen in diabetic nontransgenic mice; and normal glomeruli were seen in diabetic and non-diabetic growth hormone antagonist transgenic mice as well as non-diabetic nontransgenic littermates. These results suggest that growth hormone is playing a role in diabetic nephropathy, and elevated levels of growth hormone can directly affect the kidneys independent of the levels of glucose and glycated hemoglobin.
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PMID:A growth hormone antagonist protects mice against streptozotocin induced glomerulosclerosis even in the presence of elevated levels of glucose and glycated hemoglobin. 889 92

Proximal tubular dysfunction may be implicated in the pathogenesis of diabetic nephropathy. An investigation of proximal tubular function was carried out by assessing proximal tubular sodium-reabsorption and low molecular weight protein excretion in a group of patients with type 1 diabetes mellitus. Normoalbuminuric [group A, n = 6, albumin excretion rate (AER) mean (range) 4 (0-10) micrograms/min], and microalbuminuric [group B, n = 6, AER 88 (35-198) micrograms/min] patients with type 1 diabetes were compared with matched controls. Simultaneous lithium and growth hormone (GH) clearance and urinary beta 2-microglobulin excretion were assessed. Fasting plasma glucose at the start of the study was [median (range)] 13 (10.2-15.1), 9.3 (5.9-15) and 4.1 (4.0-5.0) mmol/l in groups A, B and controls, respectively, with a mean coefficient of variation during the study of 3.9% (group A) and 5.2% (group B). There was no significant difference in plasma glucose levels between patients in groups A and B. Urinary GH excretion was raised in the patients with microalbuminuria (group B; P < 0.05), although there was no difference in serum GH clearance rate between the patient groups and controls. Urinary GH correlated with B 2-microglobulin in the diabetic subjects (r = 0.665, P < 0.05) and with the degree of microalbuminuria in group B patients (r = 1, P < 0.01). Urinary GH was also greater than 10 microU, the median value observed in the controls, in 5 of 6 (83%) patients in group A. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) measured by constant infusion of 51Cr-ethylene diamine tetra-acetic acid (EDTA) and I125-para-amino hippuric acid (PAH), respectively, showed relative hyperfiltration in the normoalbumiruric group compared with controls (P < 0.05) and group B (P < 0.05). Absolute proximal reabsorption of sodium and of water (APRNa and APRH2O) was significantly higher in group A patients (P < 0.05). Although GFR was significantly higher in group A patients, no differences were found in fractional proximal reabsorption of sodium and water (FPRNa+H2O) or end proximal delivery between the patient groups and controls. Therefore, the measurement of protein reabsorptive capacity provides a more sensitive marker of renal tubular impairment in type 1 diabetes than sodium/fluid reabsorptive capacity. In patients with microalbuminuria, both glomerular and tubular damage may coexist. Our results stress the usefulness of markers of renal tubular function in monitoring the course of diabetic nephropathy. This study also shows that assessment of GH clearance has promise as a marker of renal tubular protein reabsorptive capacity.
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PMID:Proximal tubular reabsorption of growth hormone and sodium/fluid in normo- and microalbuminuric insulin-dependent diabetes mellitus. 913 54

Among other neuropeptides and neurohormones, growth hormone (GH) and somatostatin (SRIF) have been shown to modulate the development of glomerular injury in various renal diseases. In particular, GH is implicated in the induction of glomerular hypertrophy and sclerosis in partial nephrectomy and diabetic nephropathy. While GH effects on glomerular hypertrophy are likely mediated by insulin-like growth factor I (IGF-I), GH effects on glomerular sclerosis are independent of IGF-I. Those effects rather require multiple signaling pathways functioning in series, e.g. angiotensin II binding preceding transforming growth factor beta (TGF-beta) release, or pro-inflammatory factor release preceding repair/scarring processes. In contrast with GH, SRIF administration prevents the development of glomerular lesions in experimental diabetes, partial nephrectomy and immune glomerulonephritis. Inhibitory effects of SRIF on glomerular hypotrophy may be through a decrease in GH secretion and/or IGF-I expression or through a direct blockade of glomerular cell proliferation. The mechanisms underlying the anti-inflammatory effects of SRIF are most likely a deactivation of inflammatory cells related in part to an upregulated response of these cells to glucocorticoids. Additional studies will be required to further define the role of GH and SRIF in the development of glomerular injury and, hence, to identify new targets for a therapeutic approach in glomerular diseases.
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PMID:Growth hormone and somatostatin in glomerular injury. 1020 98

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.
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PMID:Growth hormone receptor antagonism prevents early renal changes in nonobese diabetic mice. 1054 Dec 97

Porcine growth hormone was administered subcutaneously to beagle dogs at doses of 0.025, 0.1, and 1 IU/kg/d for 14 weeks, markedly elevating serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. This was accompanied by a significant increase in body weight gain and kidney weights in both male and female dogs. The increase in kidney weight (6 to 54%) was slightly greater than the increase in body weight (6 to 40%). By light microscopy, glomerular deposits, mesangial thickening, and very slight cellular infiltration in glomeruli were seen in mid- and high-dose groups. Based on morphometric evaluation, there was an increase in the renal glomerular area, which was statistically significant (p < or = 0.05) in the mid- and high-dose males and in the high-dose females. This was associated with a statistically significant (p < or = 0.05) increase in the number of total glomerular cells in the mid- and high-dose males. By transmission electron microscopy, thickening of the glomerular basal lamina and diffuse increase of the mesangial matrix were observed in both male and female dogs in the mid- and high-dose groups. Immunohistochemical reactions were negative for IgG, IgM, and C3. The morphological changes in the kidney of dogs resemble the diffuse glomerulosclerosis described in human diabetic nephropathy.
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PMID:Morphological changes in the kidney of dogs chronically exposed to exogenous growth hormone. 1093 36

The development of diabetic nephropathy in patients with Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus is still a huge clinical problem associated with increased morbidity and mortality. The mechanisms underlying the development of diabetic kidney disease are extremely complex and yet not completely understood. Among many potential pathogenic mechanisms responsible for the development of diabetic kidney disease, various growth factors have been suggested to be important players. In particular, growth hormone (GH)/insulin-like growth factors (IGFs), transforming growth factor beta (TGF-beta), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) have measurable effects on the development of experimental diabetic kidney disease through complex intra-renal systems. Recent findings that these growth factors might initiate the early diabetic renal changes have provided insight into processes that might be relevant for future development of new drugs useful in the treatment of diabetic kidney disease. As will appear from the present review, enhanced understanding of the cellular mechanisms responsible for the development of diabetic kidney disease has already allowed the design of specific antagonists of pathophysiologically increased growth factors. Recent studies have shown that treating experimental diabetic models with such antagonists is followed by renoprotection.
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PMID:Putative pathophysiological role of growth factors and cytokines in experimental diabetic kidney disease. 1107 38

The exact mechanisms by which growth hormone (GH) damages the kidney inducing diabetic nephropathy has not yet been elucidated. Recently, it has been shown that transferrin has the same diabetogenic effects of GH, being its mediator. Transferrin was studied using immunohistochemistry and immunoelectron microscopy in cases of early diabetic nephropathy, and in controls. Transferrin was only found in diabetic cases in podocytes and Bowman's capsule cells, but also in the tubular cells of both diabetic and non-diabetic controls. Immuno-electron microscopy for the presence of transferrin showed positive signals in the cytoplasm of diabetic podocytes, but not in pedicels. This selective deposition was associated with signs of organelle and cytoskeleton damage. On the basis of previous evidence and present glomerular findings, these results suggest an indirect diabetogenic effect on the kidney by GH mediated through transferrin.
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PMID:Diabetogenic transferrin damages podocytes in early human diabetic nephropathy. 1129 98


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