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

To determine the possibility that intestinal mucosal ornithine decarboxylase activity can modulate mucosal brush border membrane Na(+)-H+ exchange activity, we studied the relationship between jejunal mucosal ornithine decarboxylase activity and mucosal brush border membrane Na(+)-H+ exchange activity in adolescent streptozotocin-diabetic and normal control rats. Diabetes was associated with enhanced intestinal mucosal ornithine decarboxylase and Na(+)-H+ exchange activities. Groups of diabetic and control rats were given difluoromethylornithine in drinking water to suppress intestinal mucosal ornithine decarboxylase activity. As expected, 10 days after induction of diabetes, intestinal mucosal weight (67.7 mg/cm vs 56.1 mg/cm), DNA (47.3 micrograms/mg protein vs 32.7 micrograms/mg protein), ornithine decarboxylase activity (1107 units/hr vs 654 units/hr), and brush border membrane vesicle Na(+)-H+ exchange activity, assessed as Vmax of 22Na+ uptake (32.5 nmol/mg protein/15 min vs 15.2 nmol/mg protein/15 min), were significantly greater in diabetic than in control rats. Treating diabetic and control rats with difluoromethylornithine suppressed jejunal mucosal growth by over 30%, ornithine decarboxylase activity by over 80%, and brush border membrane vesicle 22Na+ uptake by over 60%. Highly significant direct correlations (r > 0.900) were observed between jejunal DNA content, mucosal ornithine decarboxylase activity, and brush border membrane vesicle Na(+)-H+ exchange activity. The above findings suggest that jejunal mucosal ornithine decarboxylase activity can modulate mucosal epithelial proliferation and mucosal brush border membrane Na(+)-H+ exchange activity.
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PMID:Intestinal mucosal ornithine decarboxylase and brush border membrane vesicle Na(+)-H+ exchange activities in diabetic rats. 841 71

In this article, we have discussed the localization of components of the renal renin-angiotensin system, as well as the existing information on the regulation of this axis and the effects of Ang II on renal function. All the components of the renin-angiotensin system are present in both fetal and adult kidney. In the adult kidney, renin is principally localized to jg cells of the distal afferent arteriole, where release is stimulated by increases in intracellular cAMP and inhibited by increases in cytosolic calcium. Four distinct stimuli mediating renin release are (1) NaCl sensed at the macula densa, (2) the sympathetic nervous system, (3) humoral factors, with Ang II, vasopressin, endothelin, and adenosine inhibiting renin release, and (4) changes in intrarenal blood pressure. Alterations in renal renin gene expression have been reported in pathophysiological states, such as salt depletion, diabetes mellitus, ureteral obstruction, Bartter's syndrome, and with high protein feeding. The highest renal concentrations of mRNA for the renin substrate angiotensinogen are found in the PT, where the protein is localized to subapical granules. Both salt depletion and androgens upregulate renal angiotensinogen mRNA. Of interest, renal angiotensinogen mRNA levels are lower in SHR than in normotensive WKY rats. As with angiotensinogen, renal ACE is mainly localized to the PT, with highest concentration on the brush border. The mechanisms of regulation of both renal angiotensinogen and ACE require further study. Using recently developed specific nonpeptide Ang II receptor antagonists, it appears that adult renal Ang II receptors are principally of the AT1 class, whereas fetal kidney Ang II receptors are of the AT2 subtype. By binding to AT1 receptors, Ang II exerts constrictive effects on both afferent and efferent arterioles, with increased effect reported on efferent arterioles. Glomerular Ang II receptors are localized to mesangial cells, mediating contractile responses resulting in changes in glomerular surface area and Kf, and potentially regulating mesangial sieving and phagocytosis. These receptors are reduced with salt restriction or in experimental diabetes. The highest concentrations of tubular Ang II receptors are found in PT, on both brush border and basolateral membranes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The intrarenal renin-angiotensin system. 843 83

Early tubular alterations were studied in 53 children with insulin-dependent diabetes mellitus (IDDM), 32 of whom were followed at regular 6-monthly intervals for 3 years. The urinary levels of retinol-binding protein (RBP), beta 2-microglobulin and brush border antigens (BBA) (determined by monoclonal enzyme immunoassay) were taken as indices of functional and cellular tubular alterations; urinary albumin was considered an early marker of glomerular alterations. All indices of tubular alterations were higher in IDDM children than in 368 normal children, while albuminuria was unchanged. Urinary levels of BBA, however, varied widely during follow-up, with 25 of the 32 IDDM patients who were followed at regular intervals having pathological values for BBA on at least one occasion, followed by normalization. Metabolic alteration was found to be the main cause of this variability, since a high statistical correlation was found between urinary BBA and fructosamine (P < 0.001) and between RBP and the stable fraction of glycosylated haemoglobin (P < 0.001). The data confirm that transient tubular proteinuria occurs in diabetic children before any other marker of renal involvement such as microalbuminuria. The maintenance of good metabolic control is essential to normalize this early abnormality that can be considered a reversible sign of functional renal involvement.
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PMID:Reversible tubular proteinuria precedes microalbuminuria and correlates with the metabolic status in diabetic children. 843 75

The objective of this study was to determine whether streptozotocin-induced diabetes mellitus in the rat causes alterations in the lipid composition and fluidity of renal brush border membranes (BBM) and basolateral membranes (BLM). Compared to membranes of non-diabetic rats, BBM and BLM of diabetic rats contained 31% and 26%, respectively, less arachidonic acid and 36% and 46%, respectively, more linoleic acid esterfied in phospholipids. These changes were accompanied by a decrease in the average number of double bonds per mole of fatty acid, a measure of fatty acid unsaturation. In diabetic rats BLM had a higher total phospholipid/protein ratio (567 +/- 20 vs. 482 +/- 15 nmol/mg protein, P < 0.01), less cholesterol (369 +/- 30 vs. 512 +/- 34 nmol/mg protein, P < 0.01), more phosphatidylcholine (+72%) and less sphingomyelin (-22%) than did BBM. These differences were identical to those observed between BLM and BBM of non-diabetic rats. In control rats BLM was more fluid than BBM as assessed by the steady state fluorescence anisotrophy of diphenylhexatriene and by glycerol permeability. In diabetic rats the fluidity of BLM was not different from that of BBM as assessed by the steady state fluorescence anisotrophy of diphenylhexatriene whereas BLM was slightly more fluid than BBM as assessed by glycerol permeability. By both measures BLM and BBM from diabetic rats were significantly less fluid than BLM and BBM from control rats. Removal of proteins and cholesterol in sequence was accompanied by an increase in membrane fluidity in both groups. However, in no instance did the removal of proteins or cholesterol abolish the difference between the fluidity of diabetic membranes and that of control membranes. From these data we conclude that the reduction in fluidity of renal BLM and BBM in the diabetic rat is due to the change in the composition of fatty acids esterified in membrane phospholipids.
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PMID:Biophysical and biochemical alterations of renal cortical membranes in diabetic rat. 844 15

The authors report on a infant who presented with an auto-immune enteropathy characterized by the association of a protracted diarrhea, a neonatal insulin-dependent diabetes, and a dermatitis and who developed a nephrotic syndrome at 4 months of age. A renal biopsy showed a membranous glomerulonephritis (MGN) with IgG linear deposits along the tubular basement membranes (TMB). By indirect immunofluorescence anti-enterocyte antibodies together with anti-TMB antibodies and anti-renal brush border (BB) antibodies were found in the serum of the patient. The patient received various immunosuppressive drugs that failed to improve the disease. In the course of the disease the anti-TBM antibodies disappeared progressively but the BB antibodies persisted. A review of the literature indicates that renal involvement is not uncommon in auto-immune enteropathy and in 5 cases it has been reported as being characterized by a nephrotic syndrome related to the presence of a MGN. In 4 of these cases MGN was associated with the presence of anti-TBM antibodies and in the remaining one with anti-BB antibodies. This case report shows that in human pathology, auto-antibodies to BB proteins may, as well as in experimental models, be responsible for the development of a MGN. It suggests a close relationship (probably a common epitope) between the renal BB proteins and the proteins of the gut epithelium.
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PMID:[Renal involvement in autoimmune enteropathies]. 845 29

Preparations of isolated rat jejunal enterocyte and brush-border and basolateral membrane vesicles have been used to study the effects of a 15 min exposure of upper and mid-villus enterocytes to pancreatic glucagon on the initial, unidirectional phlorhizin-sensitive (brush border) transport of galactose and phlorhizin-insensitive (basolateral) movement of the sugar. These acute effects of glucagon have been compared with responses following treatment of animals for 1 or 3 days with the hormone. Incubation of cells with glucagon significantly stimulated phlorhizin-sensitive uptake by 42 and 64% for upper and mid-villus cells, respectively. Glucagon, however, was without effect on phlorhizin-insensitive galactose uptake. This differential action of the hormone at the two cellular loci was confirmed by uptake data obtained using purified brush-border and basolateral membrane vesicles prepared from isolated cells. In contrast to the acute challenge with glucagon, treatment of animals for 3 days with the hormone significantly increased both phlorizin-sensitive (upper villus +31%, mid-villus +74%) and phlorizin-insensitive (upper villus +42%, mid-villus +53%) galactose uptake. Glucagon exposure of exposure of isolated cells from 3 days treated animals was without further effect on galactose uptake at the two membrane loci. These data represent the first evidence for a direct action of pancreatic glucagon on enterocyte sugar transport. Thus the hormone is likely to be important in the physiological control of sugar absorption in addition to its possible role in the modulation of transport during starvation and diabetes mellitus, conditions characterized by hyperglucanonaemia and enhanced intestinal sugar transport.
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PMID:Acute and chronic effects of pancreatic glucagon on sugar transport across the brush-border and basolateral membranes of rat jejunal enterocytes. 847 Dec 40

The treatment of Type II diabetes (NIDDM) includes an appropriate diet and prudent exercise program. If these measures are insufficient to control the blood sugar, oral agents (sulphonylureas or biguanides) or insulin are added to the therapeutic regimen. Although the diet prescription has undergone some changes and refinements, this approach has been the traditional treatment for NIDDM for nearly 40 years. Recently a new class of oral agents, the alpha-glucosidase inhibitors, has become available. These drugs are competitive inhibitors of the alpha-glucosidase enzymes in the brush border of the bowel wall. They act to slow and delay the rate of carbohydrate absorption, thereby decreasing postprandial hyperglycemia. A recent study was designed to evaluate the long-term efficacy of acarbose, an alpha-glucosidase inhibitor, in improving the glycemic control of patients with NIDDM who were sub-optimally controlled on either diet alone, or diet plus sulphonylurea, metformin or insulin. A total of 354 patients with NIDDM were studied, 77 on diet alone, 83 on metformin, 103 and sulphonylurea and 91 on insulin. Subjects in each treatment stratum were randomized, double-blind to either acarbose or placebo, for 1 year. At baseline and every 3 months thereafter, fasting and postprandial glucose and C-peptide, HbA1c and fasting lipids were measured. Compared to placebo, acarbose treatment resulted in a decrease in mean postprandial glucose in all four strata (19 +/- 0.8 to 15.3 +/- 0.7 mmol/l: P < 0.001). This effect was even more pronounced and highly statistically significantly different when comparing the postprandial plasma glucose incremental area under the curve between placebo and acarbose treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1995 Aug
PMID:Acarbose for the treatment of type II diabetes: the results of a Canadian multi-centre trial. 852 10

The small intestinal sodium dependent absorption of D-glucose has been known to be increased by diabetes mellitus. Furthermore, we previously showed that the enhanced activity of Na+/glucose cotransporter (SGLT1) was restored by the treatment with insulin. The present study was designed to investigate the mechanism by which diabetes mellitus and insulin regulated the activity of the small intestinal SGLT1. The acute diabetes at 2 weeks after the injection of streptozotocin increased the expression of SGLT1 protein in rat small intestinal brush border membrane vesicles without changing the mRNA level for SGLT1. In addition, we showed that the increased content of SGLT1 protein was restored by the subcutaneous treatment with insulin. In contrast, there was no change of the mRNA level for SGLT1 in diabetic and insulin-treated diabetic rats. These results suggest that rat intestinal SGLT1 activity is under the translational or posttranslational controls by insulin.
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PMID:Evidence for the regulation of small intestinal Na+/glucose cotransporter by insulin. 865 85

In most cases of glomerulonephritis (GN) long-term course lead to chronic renal failure. The cause of inevitably gradually progress of GN to end-stage renal disease (ESRD) is unclear. The histological abnormalities seen in patients with progressive renal failure consist of focal and segmental glomerulosclerosis and tubulointerstitial nephritis. At present it is considered that tubulointerstitial changes attends almost all forms of progressive glomerular and vascular injury. It was known that chronic tubulointerstitial nephritis is characterized morphologically by tubular atrophy, interstitial fibrosis and interstitial inflammation of variable severity. The pathomechanism of this changes is complicated. Tubular ischaemia results from obliteration of peritubular capillaries, adaptation of tubular function with increased oxygen consumption and increased glomerular capillary permeability to macromolecules are reasons of chronic tubular damage. Injured tubules release growth factors and cytokines, which induce interstitial fibroblast proliferation, chemo-attraction and proliferation of infiltrating cells, and disruption of the balance between synthesis and degradation of cellular constituents. The consequences of these processes are tubular atrophy and interstitial fibrosis. Because of many studies concurred that tubulointerstitial changes determinant the progression of GN, tubular injury markers were searched for. Although over 50 enzymes were detected in human urine, only a few have been used for diagnosis in renal disease. The most widely used are lysosomal enzyme N acetyl-beta-D-glucosaminidase (NAG) and brush border enzymes alanine-aminopeptidase (AAP) and gamma-glutamyltransferase (GGT). tubular damage in hypertension, diabetes and in diagnostics of renal disease. AAP and GGT, brush border enzymes seem to be sensitive markers of renal injury too. Pathological value of GGT was observed even in the early stage of disease. Measurement of urinary excretion of low molecular weight proteins was valuable supplement in estimation of tubulointerstitial system malfunction. These proteins are readily filtered by normal glomeruli and virtually completely reabsorbed by normal proximal tubules. Favour are alpha-1-microglobulin (alpha-1-m) and retinol-binding protein (RBP) because they are less affected than beta-2-microglobulin (beta-2-m) by low urine pH. Above presented review confirm that further research in correlation between activity of disease, histological picture, deterioration in renal function and changes in urinary excretion of markers proteins (for example alpha-1-m, AAP, NAG, GGT) is advisable, and can contribute to use in clinic diagnostics of GN.
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PMID:[The role of tubulointerstitial changes in progression of kidney function failure in patients with chronic glomerulonephritis (GN)]. 875 11

Changes in membrane expression of sodium-dependent glucose transporter (SGLT1) and glucose transporter isoform (GLUT2) protein have been implicated in the increased intestinal glucose transport in streptozotocin-diabetes. The possible involvement of GLUT1 in the transport response, however, has not previously been studied. Using confocal microscopy on tissue sections and Western blotting of purified brush border membrane (BBM) and basolateral membrane (BLM), we have examined enterocyte expression of GLUT1 in untreated and in 1 and 21 day streptozotocin diabetic rats. In control enterocytes, GLUT1 was absent at the BBM and detected at low levels at the BLM. Diabetes resulted in a 4- to 5-fold increased expression of GLUT1 at the BLM and the protein could also be readily detected at the BBM. Insulin treatment of diabetic rats increased GLUT1 level at the BBM but was without effect on expression of the protein at the BLM.
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PMID:Streptozotocin diabetes and the expression of GLUT1 at the brush border and basolateral membranes of intestinal enterocytes. 891 90


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