UMLS:C0011849 - FACTA Search

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Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To clarify the ultrastructural changes in renal proximal tubules causing microalbuminuria in the early stage of diabetic nephropathy, three different groups of rats were prepared: rats with streptozotocin (STZ)-induced diabetes given no treatment (DMut; n = 7), rats with STZ-induced diabetes treated with insulin (DMt; n = 7), and non-diabetic rats injected with citrate buffer (control; n = 7). In each group, the laboratory findings, ATP content of the renal cortex, and the size of proximal tubule cells and their nuclei and mitochondria (MT) were determined. In two weeks after the start of the study, MT in renal proximal tubules showed diffuse enlargement in the DMut group as compared with those in the control group. Renal cortical ATP content, fractional sodium excretion (FENa), urinary excretion of beta 2-microglobulin and albumin were also increased significantly in the DMut group relative to the controls. In the DMt group, most of the examined parameters returned almost to normal. There were positive correlations between each of the following parameters: hyperglycemia and MT enlargement, MT enlargement and increased cortical ATP content, increased cortical ATP content and increased FENa, increased FENa and increased urinary excretion of beta 2-microglobulin and albumin. On the basis of these results, we conclude that mitochondrial enlargement, resulting from disturbed metabolism of ATP, may reduce active transport in renal proximal tubules, which, in turn, may impair reabsorption in the tubules. This would cause urinary excretion of low-molecular-weight proteins and microalbumin in the early stage of diabetic nephropathy.
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PMID:Correlation between mitochondrial enlargement in renal proximal tubules and microalbuminuria in rats with early streptozotocin-induced diabetes. 129 Mar 23

Glucose is reabsorbed from the glomerular filtrate in the proximal segment of the renal tubule in two stages. The first stage is uphill transport across the brush border membrane by Na(+)-glucose cotransport and the second stage is downhill transport across the basolateral membrane by facilitated diffusion. Genes for both a renal Na(+)-glucose cotransporter (SGLT1) and a renal facilitated glucose transporter (GLUT2) have been cloned and sequenced. To examine whether SGLT1 and GLUT2 colocalize to the same tubular epithelial cells in rat kidney, double-immunoperoxidase studies with dual chromogens and paraformaldehyde perfusion-fixed frozen sections of rat kidney were performed. Antipeptide antisera were prepared against rat GLUT2 (amino acids 510-522) and rabbit SGLT1 (amino acids 402-420). Proximal tubules were identified immunocytochemically with an antiserum raised against a synthetic peptide corresponding to the 21 amino acids at the COOH-terminal of the heavy chain of rat gamma-glutamyl transpeptidase, which is a proximal tubule-specific enzyme. The anti-GLUT2 antiserum strongly stained the basolateral membrane of 46% of cortical tubules, whereas the SGLT1 antiserum stained the brush border of 56% of the cortical tubules. The gamma-glutamyl transpeptidase antiserum also stained the brush border of 51% of the cortical tubules. GLUT2 and SGLT1 colocalized to 40% of cortical epithelium, but 16% of cortical epithelial cells were immunopositive for brush border SGLT1 and immunonegative for basolateral GLUT2. These gamma-glutamyl transpeptidase staining results suggest that at least 50% of the tubules in the cortex are proximal tubules and that SGLT1 and GLUT2 colocalize to most proximal tubules. The fact that SGLT1 antiserum immunoreacted with tubules unreactive to the GLUT2 antiserum suggests that either the SGLT1 epitope is conserved on a related brush border protein or that there is another GLUT transporter responsible for the exit of sugar from these proximal tubule cells.
Diabetes 1992 Jun
PMID:Colocalization of GLUT2 glucose transporter, sodium/glucose cotransporter, and gamma-glutamyl transpeptidase in rat kidney with double-peroxidase immunocytochemistry. 135 Feb 59

During the past 5 years, we have identified idiopathic hypercalciuria in five of seven patients referred for evaluation of renal glycosuria between 1985 and 1991. The children, all boys, ranged in age from 6 to 12 years. Endocrine function was normal, and none of the patients had hyperparathyroidism, hypercalcemia, renal tubular acidosis, or other secondary causes of hypercalciuria. The calcium/creatinine ratio in a fasting urine specimen was elevated in all five children who had hypercalciuria, with a mean value (+/- SD) of 0.34 +/- 0.06 (normal, < 0.2). In one child who had renal colic with spontaneous passage of gravel-like material, the idiopathic hypercalciuria persisted after 1 week on a diet containing 2000 mg of sodium and 300 mg of calcium. On the basis of studies that examined the site along the nephron responsible for hypercalciuria in rats with streptozocin-induced diabetes, we speculate that in children with renal glycosuria, there is defective reabsorption of glucose and calcium in the straight portion of the proximal tubule or in the collecting duct. It is likely that a similar mechanism accounts for the idiopathic hypercalciuria in children with diabetes mellitus.
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PMID:Hypercalciuria in children with renal glycosuria: evidence of dual renal tubular reabsorptive defects. 841 May 29

Individuals with non-insulin dependent or insulin-dependent diabetes mellitus present insulin resistance in peripheral tissues. This is reflected in a subnormal whole body insulin-dependent glucose utilization, largely dependent on skeletal muscle. Glucose transport across the cell membrane of this tissue is rate limiting in the utilization of the hexose. Therefore, it is possible that a defect exists in insulin-dependent glucose transport in skeletal muscle in diabetic states. This review focuses on two questions: is there a defect at the level of glucose transporters in skeletal muscle of diabetic animal models, and is this a consequence of abnormal insulin or glucose levels? The latter question arises from the fact that these parameters usually vary inversely to each other. Glucose transport into skeletal muscle occurs by two membrane proteins, the GLUT1 and GLUT4 gene products. By subcellular fractionation and Western blotting with isoform-specific antibodies, it was determined that isolated plasma membranes (PM) contain GLUT4 and GLUT1 proteins at a molar ratio of 3.5:1 and that an intracellular fraction (internal membranes; IM) different from sarcoplasmic reticulum contains only GLUT4 transporters. The IM furnishes transporters to the PM in response to insulin. Both transporter isoforms bind cytochalasin B in a D-glucose-protectable fashion. In streptozocin-induced diabetes of the rat with normal fasting insulin levels and marked hyperglycemia, the number of cytochalasin B-binding sites and of GLUT4 proteins diminishes in the PM whereas the GLUT1 proteins increase to a new ratio of about 1.5:1 GLUT4:GLUT1. In the IM, the levels of GLUT4 protein drop, as does the cellular GLUT4 mRNA. To investigate if these changes are associated with hyperglycemia, glucose levels were corrected back to normal values for a 24-h period with sc injections of phlorizin to block proximal tubule glucose reabsorption. This treatment restored cytochalasin B binding, restored GLUT4 and GLUT1 values back to normal levels in the PM, and partly restored cytochalasin B binding but not GLUT4 levels in the IM, consistent with only a partial recovery of GLUT4 mRNA. It is concluded that GLUT4 protein in the PM correlates inversely whereas GLUT1 protein correlates directly with glycemia. It is proposed that the decrease in GLUT4 levels is a protective mechanism, sparing skeletal muscle from gaining glucose and experiencing diabetic complications, albeit at the expense of becoming insulin resistant.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of hyperglycemia on glucose transporters of the muscle: use of the renal glucose reabsorption inhibitor phlorizin to control glycemia. 148 48

Renal protein mass increases in diabetic renal hypertrophy. Accretion of protein may be the result of increased protein synthesis and/or decreased protein degradation. The lysosomal proteases, cathepsins B and L, are key enzymes in cellular protein catabolism. To evaluate the role of protein degradation in diabetic renal hypertrophy, the activities of cathepsins B and L were measured in microdissected proximal tubule segments and in kidney cortex homogenates. In rats four and ten days following induction of diabetes by streptozotocin, the kidney weight was increased and the cathepsin activities were reduced in proximal tubule segments. Treatment with insulin prevented both changes. The liver weight in diabetic rats was decreased and the activity of cathepsins B and L was increased, while the activity in kidney cortex was reduced. This excluded that diabetes per se may be accompanied by decreased cathepsin activities independent of organ hypertrophy. Renal hypertrophy as a cause rather than as the consequence of reduced cathepsin activities was excluded by the finding of unchanged cathepsin activities in proximal tubule segments from rats with compensatory renal hypertrophy four days and ten days following unilateral nephrectomy. Decreased activities of cathepsins B and L may reflect decreased intracellular protein degradation. Decreased protein breakdown in proximal tubules may contribute to diabetic renal hypertrophy. In agreement with this interpretation are the results from rats six months following induction of diabetes. Renal hypertrophy is complete at that time. No further accretion of protein occurs and the cathepsin activities in the proximal tubule were not different from controls.
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PMID:Renal hypertrophy in streptozotocin diabetic rats: role of proteolytic lysosomal enzymes. 151 18

Insulin stimulates the Na(+)-Pi cotransport system in the brush-border membrane (BBM) of the renal proximal tubule, and an acute decrease in plasma insulin leads to a decrease in renal reabsorption of Pi. It has been proposed that insulin may play a role in the rapid renal adaptation to dietary deprivation of Pi. This hypothesis was tested using rats with low plasma insulin due to streptozotocin-induced diabetes. Both control and diabetic rats were housed in metabolic cages and fed either a normal Pi diet or a low Pi diet for 3 days. At the end of the third day, BBM vesicles were prepared from renal cortex and Na(+)-Pi cotransport was measured. At the whole kidney level, diabetic rats showed a normal adaptive response. There was a prompt and marked decrease in urinary Pi excretion when the rats ate a low Pi diet. At the BBM level, however, the adaptive response was absent. There was no increase in Na(+)-Pi cotransport in diabetic rats fed low Pi diet. Treatment of diabetic rats with exogenous insulin before feeding low Pi diet restored the adaptive increase in Pi transport by BBM. Insulin appears to be required for the adaptation of proximal tubule Pi transport to low Pi diet. In the absence of this adaptation in proximal tubule BBM, a compensatory response in the kidney may produce an increase in Pi reabsorption in later segments of the nephron.
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PMID:Renal adaptation to low-phosphate diet in diabetic rats. 159 Apr 17

Growth hormone (GH) and insulin-like growth factor I (IGF-I) exert a variety of actions in renal tissue. To shed light upon the renal GH-IGF I axis we have characterized the cell biology of GH and IGF I in two parts of the nephron that are targets for these peptides, proximal tubule and collecting duct. Receptors for both GH and IGF I are present in the basolateral membrane of the renal proximal tubular cell. GH activates phospholipase C and IGF I stimulates phosphorylation of its receptor at this site. Both peptides directly enhance gluconeogenesis in proximal tubule. GH stimulates IGF I gene expression in collecting duct. IGF I of collecting duct origin could act as a paracrine growth factor in other portions of the nephron. IGF I may be causative of renal hypertrophy that occurs in the settings of hypersomatotropism, unilateral nephrectomy (compensatory hypertrophy) and diabetes mellitus.
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PMID:Renal cellular biology of growth hormone and insulin-like growth factor I. 165 79

The expression of renin and angiotensinogen genes and their proteins were studied during the progression of diabetes using adult BioBreeding spontaneously diabetic rats at 1 day and 2-12 months of diabetes. The number of renin-stained cells per juxtaglomerular apparatus was determined by immunocytochemistry. Initially, at 2 months of diabetes the number of renin-stained cells per juxtaglomerular apparatus increased significantly (p less than 0.0001, 2 months versus resistant groups) and was followed by a decrease in the number and intensity of renin-stained cells after 12 months of diabetes (p = 0.007, 2 months versus 12 months). A significant negative correlation was observed between the number of renin-containing cells and the duration of diabetes (r = 0.99, p = 0.014). Immunoreactive angiotensinogen was restricted to the proximal tubule and appeared increased after 4 and 8 months of diabetes as compared with the 2- and 12-month diabetic groups. Renin messenger RNA (mRNA) levels increased with the onset of diabetes and decreased markedly during chronic diabetes. At 1 day of diabetes, renin mRNA levels were 700% higher than at 12 months of diabetes. Angiotensinogen mRNA levels were unchanged. We conclude that diabetes results in an initial increase in renin gene expression, and as the duration of diabetes lengthens, there is a progressive decrease in renin gene expression and in the number of cells containing renin. These findings suggest that as the duration of diabetes and the age of the animal lengthens, there is a decrease in the number of cells expressing the renin gene.
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PMID:Renin and angiotensinogen expression during the evolution of diabetes. 173 Apr 42

A sensitive quantitative radioimmunoassay is described by which different antigens in the urine can be assayed simultaneously. Urinary excretion of three proteins from proximal tubules was compared: 1) the Na+-D-glucose cotransporter from brush border membranes and subapical vesicles; 2) a kidney-specific hydrophobic M(r) 400,000 polypeptide from intermicrovillar invaginations and subapical vesicles; and 3) villin from microvilli cores. In the normal urine about 50% of the excreted Na+-D-glucose cotransporter and villin, and about 25% of the M(r) 400,000 polypeptide was associated with brush border membrane vesicles, whereas the remaining fractions of the three proteins formed small sedimentable aggregates which contained some cholesterol and fatty acids but no phospholipids. The normal urinary excretion of the Na+-D-glucose cotransporter was correlated with that of villin and the M(r) 400,000 polypeptide. The data show that membrane proteins from the proximal tubule are excreted by the shedding of different brush border membrane areas. They suggest that some microvilli are released in total, and that a large fraction of the brush border membrane proteins is excreted without being associated with a phospholipid bilayer. In an attempt to define protein excretion patterns during kidney malfunctions, the excretion of brush border membrane proteins was analyzed after one intravenous injection of the X-ray contrast medium, iopamidol. No change in villin excretion was observed, but a reversible increase in the excretion of brush border membrane proteins was found in patients without diabetes. With diabetes a more pronounced iopamidol effect on the excretion of brush border membrane proteins and a significant increase in the excretion of villin was observed.
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PMID:Analysis of Na+-D-glucose cotransporter and other renal brush border proteins in human urine. 176 86

Tubulointerstitial lesions often develop in the kidneys of patients and experimental animals with diabetes mellitus. In an in vitro model of diabetic renal disease, it has been previously demonstrated in this laboratory that elevated glucose levels stimulate procollagen transcription and secretion in proximal tubule cells in culture while inducing cellular hypertrophy and reducing cellular proliferation. Previous experiments in other tissues have suggested that myo-inositol supplementation, probably by reversing a disturbance in cell myo-inositol metabolism related to increased activity of the polyol pathway, reverses the effects of glucose on cell function. We tested the effect of myo-inositol supplementation on proximal tubule cells in culture in the presence of elevated medium glucose level. Incubation in 450 mg/dL of glucose media reduced cell proliferation; 450 mg/dL of glucose plus myo-inositol (800 microM) increased proliferation, returning the value to that seen in cells incubated in 100 mg/dL of glucose. Incubation in 450 mg/dL of glucose media increased type IV and type I procollagen mRNA levels and peptide secretion rates compared with those seen in cells incubated in medium containing 100 mg/dL of glucose. This glucose-induced stimulation of procollagen mRNA levels and procollagen secretion was not observed when the elevated glucose medium was supplemented with 800 microM myo-inositol. On the other hand, myo-inositol supplementation did not prevent the glucose-induced cellular hypertrophy: there was no reduction in the increased leucine incorporation and cellular protein content. Cell incubation in 450 mg/dL of glucose media did not lead to a measurable decrease in total cellular myo-inositol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of myo-inositol on cell proliferation and collagen transcription and secretion in proximal tubule cells cultured in elevated glucose. 193 34

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