Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kidney is a site of insulin-like growth factor I (IGF-I) production and IGF-I mediates effects on kidney growth and function. Diabetes is associated with kidney growth in man and the rat and, in the latter, commences within 48 h of induction of diabetes. Levels of kidney IGF-I are increased during the first 2-3 days of diabetes and this is at least partially due to increased production. Additionally, IGF-I binding is increased in diabetic rat kidney, due to increased binding to the IGF-I receptor and induction of proximal tubular binding protein expression. These changes are attenuated in prepubertal rats suggesting hormonal regulation. Further studies suggest that the changes are partly GH-dependent but independent of direct sex steroid effects. As kidney growth has been implicated in the subsequent development of diabetic nephropathy, further exploration of the close association between diabetes-related kidney growth and IGF-I accumulation may lead to an improved understanding of this complication.
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PMID:IGF-I and IGF binding proteins in diabetes-related kidney growth. 128 98

Insulinlike growth factor I (IGF-I) is a mitogenic hormone with important regulatory roles in growth and development. One of the target organs for IGF-I action is the kidney, which synthesizes abundant IGF-I receptors and IGF-I itself. To study the involvement of IGF-I and the IGF-I receptor in the development of nephropathy, one of the major complications of diabetes mellitus, we measured the expression of these genes in the kidney and in other tissues of the streptozocin-induced diabetic rat. The binding of 125I-labeled IGF-I to crude membranes was measured in the same tissues. We observed a 2.5-fold increase in the steady-state level of IGF-I-receptor mRNA in the diabetic kidney, which was accompanied by a 2.3-fold increase in IGF-I binding. In addition to this increase in IGF-I binding to the IGF-I receptor, there was also binding to a lower-molecular-weight material that may represent an IGF-binding protein. No change was detected in the level of IGF-I-peptide mRNA. Similarly, IGF-II-receptor mRNA levels and IGF-II binding were significantly increased in the diabetic kidney. IGF-I- and IGF-II-receptor mRNA levels and IGF-I and IGF-II binding returned to control values after insulin treatment. Because the IGF-I receptor is able to transduce mitogenic signals on activation of its tyrosine kinase domain, we hypothesize that, among other factors, high levels of receptor in the diabetic kidney may also be involved in the development of diabetic nephropathy. Increased IGF-II-receptor expression in the diabetic kidney may be important for the intracellular transport and packaging of lysosomal enzymes, although a role for this receptor in signal transduction cannot be excluded. Finally, the possible role of IGF-binding proteins requires further study.
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PMID:Experimental diabetes increases insulinlike growth factor I and II receptor concentration and gene expression in kidney. 217 8

Renal hypertrophy is a characteristic and early manifestation of diabetes in human and experimental animals. We examined the precise distribution of insulin-like growth factor-I (IGF-I) receptor mRNA in the experimental diabetic rat kidney using a nonradioactive in situ hybridization technique. Expression of IGF-I receptor mRNA was rarely seen in the glomeruli of control rats. IGF-I receptor mRNA was detected after induction of diabetes in glomerular mesangial, visceral epithelial, and parietal epithelial cells. The number of IGF-I receptor mRNA-positive cells in a glomerulus increased significantly at 4 weeks as compared with the control rats. Overexpression of IGF-I receptor in glomerular cells may contribute to the glomerular hypertrophy in diabetic nephropathy.
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PMID:Upregulation of insulin-like growth factor receptor gene in experimental diabetic rat glomeruli. 857 42

Renal hypertrophy is a characteristic and early manifestation of diabetes in humans and experimental animals. We examined the precise distribution of insulin-like growth factor-I (IGF-I) mRNA and IGF-I receptor mRNA in the experimental diabetic rat kidney using a nonradioactive in situ hybridization technique. No significant difference in the distribution of IGF-I mRNA was found between the diabetic and control rats. IGF-I mRNA-positive cells were found in the collecting ducts and in scattered single cells in the distal tubules. The number of IGF-I mRNA-positive cells was very low in the glomeruli. Expression of IGF-I receptor mRNA was rarely seen in the glomeruli of control rats. IGF-I receptor mRNA was detected after induction of diabetes in glomerular mesangial, visceral epithelial, and parietal epithelial cells. The number of IGF-I receptor mRNA-positive cells in a glomerulus increased significantly, peaking at 4 weeks as compared with the control rats. Overexpression of IGF-I receptor in glomerular cells, especially mesangial and visceral epithelial cells, may contribute to glomerular hypertrophy in diabetic nephropathy.
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PMID:Increased gene expression of insulin-like growth factor-i receptor in experimental diabetic rat glomeruli. 873 Apr 36

The non-obese diabetic mouse is a model of spontaneous insulin-dependent diabetes as a result of autoimmune destruction of pancreatic beta cells, similar to the disease seen in human Type I diabetes. This mouse strain develops glomerular lesions reminiscent of those seen in human disease. The study presented here investigated the changes in renal insulin-like growth factor (IGF) system in hyperglycemic non-obese diabetic mice. Female non-obese diabetic mice and their age- and sex-matched controls were euthanized 4 days, 2 wk, and 4 wk after the onset of glycosuria. Kidney weight increased in diabetic mice, beginning at 2 wk after the onset of glycosuria. This renal hypertrophy was associated with an increase in renal extractable IGF-I protein. However, a decrease in IGF-I mRNA was observed at the same time. Serum IGF-I levels remained stable after 2 wk of diabetes and decreased at 1 month. No change was detected in renal IGF-I receptor mRNA levels. Renal cortical IGF binding protein (IGFBP)-1 mRNA levels were increased. Ligand blot analysis revealed a significant increase in serum and renal 30-kd IGFBP and a decrease in serum and kidney IGFBP-3 and IGFBP-4 at 30 days of diabetes. Insulin therapy prevented the increases in kidney weight, renal IGF-I, and 30-kd IGFBP, but did not reverse the decreased serum IGF-I levels observed at 1 month of diabetes. In summary, renal hypertrophy in non-obese diabetic mice is associated with a persistent accumulation of renal IGF-I and, IGFBP-1. These changes were partially reversed with insulin therapy, which did not correct the hyperglycemia, suggesting an important role for insulin deficiency in mediating these changes in the IGF system. These findings suggest that the IGF system may play a potential role in the development of diabetic nephropathy.
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PMID:Renal hypertrophy in hyperglycemic non-obese diabetic mice is associated with persistent renal accumulation of insulin-like growth factor I. 907 12

Mesangial cells (MC) isolated from glomerulosclerosis-prone ragged, olygosyndactilism, pintail (ROP) mice retain a stable phenotype after exposure to elevated glucose concentrations, whereas MC from glomerulosclerosis-resistant C57BL/6 (C) mice do not. In NOD and db/db mice, the stable phenotype induced by diabetes consists of autocrine activation of the IGF-I signaling pathway. We hypothesized that high ambient glucose activates the IGF-I pathway in ROP but not in C MC. MC were propagated in either 6 or 25 mm glucose. Isolated murine glomeruli were used to confirm in vitro experiments. 25 mm glucose induced increased insulin receptor substrate (IRS)-1 phosphorylation in ROP but not C MC. However, IGF-I, IGF-I receptor, and IRS-1 protein levels were induced by exposure to 25 mm glucose in both cell lines. This occurred without a change in IGF-I binding sites, suggesting a role for IGF binding protein (IGFBP). ROP MC and glomeruli expressed less IGFBP-2 than C MC and glomeruli. Addition of exogenous IGFBP-2 partially blunted the effect of 25 mm glucose on IRS-1 phosphorylation in ROP MC. Renal biopsies from patients with diabetic nephropathy also showed markedly decreased IGFBP-2 expression when compared with patients without nephropathy. In summary, glucose induces IRS-1 phosphorylation in MC isolated from ROP mice susceptible to glomerulosclerosis. IGFBP-2 expression was low in ROP MC and glomeruli from patients with diabetic nephropathy, suggesting that this may represent a new marker of susceptibility to diabetic nephropathy. Finally, addition of exogenous IGFBP-2 in ROP MC partially blunted the effect of high glucose on IRS-1 phosphorylation and might have a protective role.
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PMID:Low insulin-like growth factor binding protein-2 expression is responsible for increased insulin receptor substrate-1 phosphorylation in mesangial cells from mice susceptible to glomerulosclerosis. 1655 65