Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effects of acute diabetes mellitus on jejunal transport of phosphate (32P) by rat brush border membrane vesicles (BBMV) using a Millipore filtration technique. Diabetes was induced by an intravenous (i.v.) injection of 50 mg/kg of streptozocin (STZ). Control and diabetic rats were studied 4 days after the induction of diabetes. In both control and diabetic rats, the presence of a sodium gradient significantly enhanced the uptake of 32P at 20 s and at 1, 2, 5, and 60 min as compared with potassium gradient conditions. Na+-dependent 32P uptake at 20 s and at 1 and 2 min was significantly greater in the diabetic BBMV compared with controls. Na+-independent 32P uptake in both diabetic and control BBMV was similar. To determine whether the enhancement of Na+-dependent 32P uptake in diabetic BBMV is due to an induction of Na+/phosphate cotransporter activity, or a change in Na+ permeability, two additional studies were conducted. Trans-stimulation studies nullifying all electrochemical gradients across the membranes were performed. In diabetic BBMV, 32P uptake at all time points was significantly greater than corresponding values in controls, indicating an increase in the activity of Na+/phosphate cotransporters. 22Na uptake into BBMV at 30 s and at 1, 2, and 60 min was not different between diabetics and controls, indicating that Na+ permeability is not altered in diabetes. Furthermore, kinetic studies using phosphate concentrations between 0.05 and 2.5 mM indicate a significant increase in Vmax capacity of diabetic rats compared with controls without a change in Km values.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Aug
PMID:Phosphate transport by jejunal brush border membrane vesicles of the streptozocin-diabetic rat. 401 14

A significant increase of the (Na+ + K+)-activated ATPase was found in mucosal homogenates of rat small intestine under conditions of alloxan and streptozotocin diabetes. From studies with isolated plasma membranes it has been shown that the activity changes were caused by that part of the (Na+ + K+)-activated ATPase only which is localized in the basolateral plasma membranes, whereas the enzyme activity in the brush border region remains unchanged. In connection with the enhanced capacity of ion, nonelectrolyte and water absorption in experimental diabetes, our findings support a concept of intestinal transport mechanism which suggest that the basolateral part of the (Na+ + K+)-activated ATPase is responsible for metabolic energy supply. The luminal part of the enzyme may be involved in regulation of passive Na+ influx.
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PMID:[Increase of (Na+ + K+)-activated ATPase activity of basolateral plasma membranes from intestinal mucosa of diabetic rats]. 630 25

In a survey the present possibilities are outlined to get knowledge about diseases of inner organs with the help of enzyme determinations in the urine. Here it is remarkable that changes of the enzyme excretion appear not only in renal disease with acute renal failure, pyelonephritis, glomerulonephritis, renal infarction and nephroptosis but are also to be observed in primarily extrarenal diseases such as diabetes mellitus, hyperthyroidism, thesaurismoses, myocardial infarction, hypertension, acute pancreatitis, epidemic hepatitis, liver cirrhosis, obstructive jaundice and rheumatoid arthritis. The causes of the changes of enzyme excretions are various. Since enzymes of different origin and localisation behave themselves variably, the simultaneous determination of a brush border marker (e.g. alanine aminopeptidase), a lysosomal enzyme (e.g. beta-glucuronidase or N-acetyl glucosaminidase) and a low molecular enzyme (e.g. lysozyme) is of use for the recognition of renal alterations. By the control of activities of urinary enzymes it is possible to get without risk informations about pathobiochemical processes in the kidney which are not to be gained by means of other methods.
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PMID:[Urinary enzyme excretion in diseases of the internal organs]. 636 87

Filtered proteins including insulin are absorbed in the proximal tubule by means of pinocytosis. The first step in this process is binding of the protein to brush border membrane. As it is not known whether absorption exhibits specificity, we set out to determine whether specific binding sites for insulin are present in brush border membranes. Rabbit-isolated brush border membranes were incubated with 125I-insulin and varying concentrations of cold insulin or other peptide hormones. Binding and degradation of 125I-insulin occurred in a time- and temperature-dependent manner. Native insulin competitively inhibited 125I-insulin binding, but calcitonin, arginine vasopressin, glucagon, and growth hormone (10(-6) M) were relatively ineffective. Nonspecific binding averaged one-third of the total radioactivity bound. Scatchard analysis of binding data revealed two classes of insulin receptors: high affinity, low capacity receptors and low affinity, high capacity receptors. Gel filtration analysis of 125I-insulin exposed to brush border membrane revealed the formation of low-molecular-weight products similar to that produced by intact kidneys. The degrading process exhibited some specificity, for cold insulin (10(-6) M) was more effective than calcitonin, vasopressin, glucagon, or growth hormone in inhibiting degradation (32% versus less than 13% inhibition; P less than 0.01). Whether this reflects inhibition of insulin specific binding before exposure to degradation or inhibition of specific enzymes is unclear. In summary, it appears that renal brush border membranes have a major insulin-specific receptor component that could potentially mediate tubular insulin absorption. In addition, there is a smaller nonspecific component that may also have the potential to mediate insulin absorption. Finally, it appears that brush border membranes have the ability to degrade insulin to low-molecular-weight products by a process that exhibits some specificity for insulin.
Diabetes 1982 Jul
PMID:Binding and degradation of insulin by isolated renal brush border membranes. 676 Dec

We examined the mechanism of myo-inositol uptake by rabbit renal proximal tubule brush border membrane vesicles and characterized the relationship between the transports of myo-inositol and D-glucose. A 100 mM Na+ electrochemical gradient (extravesicular medium > intravesicular medium) stimulated the initial rate of myo-inositol uptake 20- to 60-fold. Other cation gradients were ineffective. The Na+ myo-inositol co-transport system was shown to be electrogenic. The Na+ electrochemical gradient-dependent uptake of myo-inositol saturated at about 1 mM myo-inositol, with an apparent Km of 94 micro M at an initial 100 mM Na+ gradient. D-Glucose was an inhibitor of the Na+ gradient-dependent uptake of myo-inositol. D-Glucose, but not L-glucose, elicited accelerative exchange diffusion of myo-inositol. myo-Inositol did not significantly inhibit the Na+ gradient-dependent transport of D-glucose. We suggest that D-glucose inhibits myo-inositol uptake by dissipating the membrane potential and sharing the myo-inositol carrier. The inhibition of myo-inositol transport across the brush border membrane by D-glucose explains how glycosuria could produce inosituria in patients with diabetes mellitus.
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PMID:myo-Inositol transport in renal brush border vesicles and it inhibition by D-glucose. 677 22

Altered tissue levels of trace metals have been reported in streptozotocin-diabetic (STZ) rats. To determine whether increased hepatic and renal levels of Cu and Zn were associated with enhanced intestinal absorption, trace metal absorption was studied in control (C) and STZ rats using dietary balance and in situ ligated-loop techniques. The apparent daily absorption of dietary Zn and Cu per 100 g body wt was threefold higher in STZ than C rats. In comparison, dietary Fe absorption per day was not altered. Increased Zn absorption was closely correlated with diabetes-associated polyphagia. The initial rate of injected 65Zn excretion was more rapid in STZ rats, although the rate of excretion beyond day 7 was similar from C and STZ animals. The quantity of Zn, Fe, and Cu absorbed per 20 cm duodenal loop was similar for C and STZ rats. Zn, Fe, and Cu absorption per gram dry mucosa were reduced 45-53% in STZ rats due to the 50% increase in mucosal mass. Moreover, the quantity of radioisotopes accumulated per gram dry mucosa and the concentration of metallothionein per gram mucosal cytosol protein were similar in C and STZ animals. Together, these data demonstrate that increased absorption of dietary Zn and Cu is in part responsible for accumulation of these elements in STZ tissues and suggest altered metal transport at the luminal (brush border) surface of the intestinal epithelium.
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PMID:Zinc, iron, and copper absorption in the streptozotocin-diabetic rat. 682 72

Acarbose delays digestion of complex carbohydrates and disaccharides to absorbable monosaccharides, by reversibly inhibiting alpha-glucosidases within the intestinal brush border, thereby attenuating postprandial blood glucose peaks. Clinical trials have demonstrated that acarbose generally improves glycaemic control in patients with non-insulin-dependent diabetes mellitus (NIDDM) managed with diet alone, or with other antidiabetic therapy, as evidenced by decreased postprandial plasma glucose and glycosylated haemoglobin levels. It does not appear to directly alter insulin resistance, but may lower postprandial plasma insulin levels. Fasting plasma glucose, triglyceride and/or cholesterol levels may also be decreased. Acarbose also improved metabolic control in patients with insulin-dependent diabetes mellitus (IDDM), frequently decreasing insulin requirements, although further studies are required in this indication. Improved metabolic control appears to delay or prevent long term vascular complications of diabetes, and indeed, acarbose appeared to inhibit development of such complications in preliminary animal studies, but this finding requires confirmation in clinical studies. While acarbose seldom causes systemic adverse effects, it is associated with a high incidence of gastrointestinal disturbances such as flatulence, abdominal distension, borborygmus and diarrhoea, caused by fermentation of unabsorbed carbohydrates. However, these symptoms tend to subside with continued treatment and adherence to an appropriate diet. Thus, acarbose appears to be a worthwhile adjunctive therapeutic option for patients with NIDDM inadequately managed by diet alone, or with pharmacological therapy, and possibly also for patients with IDDM. However, further long term efficacy and tolerability data are required, particularly in the latter indication.
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PMID:Acarbose. An update of its pharmacology and therapeutic use in diabetes mellitus. 751 Jun 10

The diabetes-associated changes in intestinal uptake of nutrients are modified by isocaloric alterations in the type of dietary lipids, and is associated with alterations in the phospholipid and fatty acyl content of the intestinal brush border membrane. We wished to test the hypothesis that diet- and diabetes-associated changes in brush border membrane phospholipid fatty acids are due to alterations in the activity of enterocyte microsomal delta-5, delta-6 and delta-9 desaturases. Adult female Wistar rats were divided into two groups. In half of the animals, diabetes was produced with the injection of streptozotocin, and the other half of the animals served as nondiabetic controls. Both groups were raised on chow for two weeks and were then randomized to one of four semisynthetic diets for two weeks: beef tallow low in cholesterol (BT), beef tallow high in cholesterol (BTC), fish oil low in cholesterol (FO), or fish oil high in cholesterol (FOC). Feeding a high cholesterol diet increased the activity of jejunal enterocyte microsomal membrane activity of delta-5 and delta-9-desaturases when fed with FO in non-diabetic control rats, increased delta-5-desaturase in diabetic rats fed FO, and increased the ileal activity of delta-5 and delta-6-desaturases in control and diabetic animals fed FO. Dietary fatty acids, cholesterol and diabetes did not produce the changes in the amount of fatty acids in BBM phosphatidylcholine or phosphatidylethanolamine expected from the measured alterations in delta-5 (20:4 omega 6 and 20:5 omega 3), in delta-6 (18:3 omega 6 and 18:4 omega 3), or in delta-9 desaturase (18:1 omega 9 and 16:1 omega 7). In summary, 1) the activities of enterocyte microsomal membrane delta-5, delta-6 and delta-9-desaturases are independently influenced by dietary fatty acids or cholesterol, or by diabetes; 2) changes in dietary fatty acids, cholesterol and diabetes are associated with alterations in the fatty acyl constituents of brush border membrane phosphatidylcholine and phosphatidylethanolamine, but these fatty acyl changes are not explained on the basis of variations in the activities of the microsomal desaturases. Thus, the intestinal brush border membrane and the enterocyte microsomal desaturases are capable of adapting in response to changes in dietary lipids or diabetes, but the two alterations are not necessarily causally interrelated.
Diabetes Res 1994
PMID:Dietary omega-3 fatty acids and cholesterol modify desaturase activities and fatty acyl constituents of rat intestinal brush border and microsomal membranes of diabetic rats. 755 26

Glucose uptake is increased into the intestine of diabetic rats, and this adaptation can be modified further by manipulation of the type of fatty acids in the triglycerides in the diet. Jejunal brush border membrane vesicles were used to examine the uptake of D-glucose into the jejunum of non-diabetic control and streptozotocin-diabetic rats fed for two weeks in isocaloric semisynthetic diet enriched with saturated fat (beef tallow) or polyunsaturated omega-3 fatty acids (fish oil). The time-course of uptake of 100 microM glucose demonstrated an overshoot which peaked at approximately 30 seconds and declined thereafter to an equilibrium plateau. In concentration studies, glucose uptake was greater into brush border membrane vesicles of diabetic as compared with control rats. The maximal transport rate (Vmax) was increased approximately 9-fold in diabetics as compared with control rats fed beef tallow (p < 0.05), and was increased approximately 6-fold in diabetic rats fed fish oil. In diabetic rats, feeding fish oil reduced the value of the Vmax by approximately 50% as compared with diabetic rats fed beef tallow. Thus, the enhanced glucose uptake into BBM vesicles of streptozotocin-diabetic rats can be partially corrected by feeding an isocaloric semisynthetic diet enriched with polyunsaturated omega-3 fish oils.
Diabetes Res 1994
PMID:Feeding an isocaloric omega-3 fatty acid diet reduces the brush border membrane vesicle uptake of glucose in streptozotocin-diabetic rats. 764 81

1. We investigated the mechanism of decreased transmucosal calcium transport in the gut of the diabetic rat by comparing calcium uptake by brush border membrane vesicles from control and streptozotocin diabetic rats at 5 days. Brush border calcium uptake consists of saturable and non-saturable components. Saturable uptake is mediated by a specific mobile carrier mechanism and is defined by Vmax (saturable uptake of calcium at infinite medium calcium concentration) and KT (calcium concentration at Vmax/2). Non-saturable uptake is defined by kD (rate constant for non-saturable uptake per unit calcium concentration), and comprises both diffusive and surface binding components of calcium uptake. 2. We found both saturable and non-saturable calcium uptake to be decreased (P < 0.05) in diabetes. Comparing control and diabetic, Vmax was 247 compared to 152 (data are pmol/mg protein per 3 s); kD was 285 compared to 172 (data are pmol/mg protein per 3 s at 1 mmol/L calcium); and KT (mmol/L) did not differ between groups, 0.070 compared to 0.057. 3. The decreased Vmax in the setting of unchanged KT in vesicles from diabetics is consistent with decreased calcium transporter specific activity, rather than with altered transporter function. 4. Since (i) Vmax is decreased by vitamin D deficiency in the normal rat, and (ii) circulating 1 alpha, 25-dihydroxycholecalciferol is decreased in the diabetic rat, decreased Vmax in the diabetic may be related to the low 1 alpha,25-dihydroxycholecalciferol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of diabetes on calcium uptake by rat brush border membrane vesicles. 767 39


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