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

The present work was designed to identify the HCO3(-)-dependent alkalinizing carrier in ventricular myocytes of normal and diabetic adult rats and to determine to what extent this system contributes to acid-equivalent extrusion after an intracellular acidification. We also examined the possible influence of intracellular Ca2+ (Cai2-) and glycolytic inhibition on the carrier activation. Intracellular pH (pHi) was recorded using seminaphthorhodafluor-1. The NH4+ method was used to induce an intracellular acid load. Evidence is provided for the existence of a Cl(-)-independent Na(+)-HCO3- cotransport contributing to pHi recovery from an intracellular acid load in ventricular cells of adult rats. Na(+)-HCO3- cotransport accounts for 33% of the total acid-equivalent efflux (JHe) from normal adult myocytes after intracellular acidification at pHi 6.75 in CO2/HCO3(-)-buffered solution. In addition, the activity of this carrier, which is not affected either by decreasing Cai2+ or by inhibiting Ca2+/calmodulin protein kinase II, is down-regulated by inhibition of glycolysis. Under pathophysiological conditions such as diabetes, although total JHe was significantly decreased compared with normal myocytes, JHe carried by Na(+)-HCO3- cotransport remained unchanged. However, because of a decrease in Na+/H+ exchange, the contribution of this carrier to total JHe increased with decreasing pHi (i.e., under conditions that may be associated with an ischemic episode), reaching approximately 58% of total JHe at pHi 6.75 (vs. approximately 33% in normal myocytes.
 ...
PMID:HCO3(-)-dependent alkalinizing transporter in adult rat ventricular myocytes: characterization and modulation. 943 92

The chloric acid method is most commonly used to obtain accurate and reproducible measurements of iodine and removes interfering substances. Unfortunately, chloric acid is a potential hazard requiring an explosion proof hood among other precautions. We have developed a simple, convenient, and economic method for measuring urinary iodine using 1 mol/L ammonium persulfate, a non-explosive, non-hazardous chemical, as the oxidizing reagent. The oxidation procedure can be completed in 30 minutes at a temperature of 91-95 degrees C. The iodine in the urine is then measured by a modification of the traditional colorimetric method of Sandell-Kolthoff. 110 urine samples collected from a mixed population of healthy males and females, ranging in age from 6 to 79 years and living in the United States were analyzed for iodine content by two methods: the proposed ammonium persulfate method and the chloric acid method. The ammonium persulfate method has an intra assay CV of 9.1% at 0.42 +/- 0.04 micromol/L (mean +/- SD), 7.8% at 1.46 +/- 0.11 micromol/L and 4.0% at 3.54 +/- 0.14 micromol/L. The inter assay CV is 10.2% at 0.46 +/- 0.05 micromol/L and 7.9% at 3.27 +/- 0.26 micromol/L. Recovery of iodine added to urine in vitro was 107%, 94% and 97% for 0.42 micromol/L, 0.77 micromol/L and 3.64 micromol/L, respectively. The lower limit of detectability was 0.0034 microgI. Values for iodine in 110 urines measured by the reference chloric acid method ranged from 0.06 to 8.03 micromol/L and by the ammonium persulfate method from 0.05 to 7.4 micromol/L. The persulfate method (y) correlated extremely closely with the reference chloric acid method (x) by the Pearson correlation (y = 0.923x + 0.810 micromol/L, and r = 0.994, Syx = 1.841). In conclusion a new, safe, simple method for measuring urinary iodine is described which uses ammonium persulfate as the oxidizing agent for the removal of interfering substances.
Exp Clin Endocrinol Diabetes 1998
PMID:Ammonium persulfate: a new and safe method for measuring urinary iodine by ammonium persulfate oxidation. 986 49

This work describes an optimization of a simple photometric determination of iodine concentrations in urine using a modified ceric arsenite method with ammonium persulfate as oxidant. By means of this sensitive method iodine concentrations can be determined in very small specimens (50 microL). Urine samples (105) collected from a mixed population, were analyzed for urine iodine content by the optimized ammonium persulfate method, a Technicon Autoanalyzer II and a paired-ion-RP HPLC. We found that the precision of this optimized ammonium persulfate method yields inter assay CVs of <10% for urinary iodine concentrations >10 microg/dL. Recovery of [123I]iodide added to urine in vitro was 100.9 +/- 2.4%. The detection limit was 0.0029 microg iodine. There was a high correlation between all three methods (r > 0.94 in any case) and the interpretation of the results was consistent. We conclude that this simple, manual ammonium persulfate method is suitable for urinary iodine analysis and can be performed in any routine clinical laboratory.
Exp Clin Endocrinol Diabetes 1998
PMID:Methodological and analytical aspects of simple methods for measuring iodine in urine. Comparison with HPLC and Technicon Autoanalyzer II. 986 50

The most important information in the determination of the status of iodine nutrition of a population comes from the measurement of the urinary excretion of iodine. Several methods are available for measuring urinary iodine. The choice among methods depends on the intended application, the number of samples, the cost and the technical capability. Epidemiological field studies demand simple, rapid and cost-effective methods. Suitable for these applications are the rapid urinary iodide test and the ammonium persulfate oxidation method which gives comparable results to the chloric acid method without having the drawbacks of being hazardous and explosive. In research studies however, sophisticated automated technology like the Technicon Autoanalyzer or Paired-Ion Reversed Phase HPLC are used in which the high cost of instrumentation are outweighed by the benefits of processing a large number of samples with high accuracy and minimal technician time. For determining serum inorganic iodide (SII) the HPLC assay is the method of choice, because contaminations from the protein bound iodine fraction do not interfere with the detection process. The clinical relevance of the measurement of SII is limited, but allows the calculation of the absolute iodine uptake which has great value in pathophysiologic studies.
Exp Clin Endocrinol Diabetes 1998
PMID:Methods for measuring iodine in urine and serum. 986 94

ZD7114, [(S)-4-[2-(2-hydroxy-3 phenoxypropylamine)ethoxy]-N-(2-methoxyethyl) phenoxyacetamide], and ZD2079, [(R)-N-(2-[4- (carboxymethyl)phenoxy]ethyl)-N-(beta-hydroxyphenethyl)ammonium chloride], are beta 3-adrenoceptor stimulants with selectivity for brown adipose tissue. ZD7144 is the hydrochloride salt of the S-enantiomer of the racemic amide ZD2079. They were developed as potential novel treatments for obesity and non-insulin-dependent diabetes mellitus. Male and female rats were dosed separately by gavage for a minimum of 28 days with 0, 10, 50, and 500 mg/kg/day of ZD7114 or with 0, 10, 30, and 150 mg/kg/day of ZD2079. Two further groups of male and female rats were dosed with 0 and 500 mg/kg/day of ZD7114 for 28 days and were then allowed a 6-wk, undosed withdrawal period. At high doses, both compounds caused urinary tract toxicity, which primarily affected the distal tubules and collecting ducts of the kidney via tubular necrosis. They also caused ureteric inflammation, cystitis, and accumulation of crystalline inclusions throughout the urinary tract. As a result of urinary tract toxicity, affected animals from one or both studies showed reduced red blood cell indices, lower platelet counts, and higher white cell counts. Blood chemistry revealed lower plasma concentrations of glucose (7.28 +/- 1.37 compared to 8.11 +/- 0.65 for the control) and total protein (63.42 +/- 3.65 compared to 69.17 +/- 3.24 for the control) and increased plasma urea (37.15 +/- 19.96 compared to 8.09 +/- 0.87 for the control). Urinalysis showed an increase in the number of crystals, blood, and protein. In the urinary tract, the severe crystalluria with accumulation of crystalline material indicated that this may have a role in the etiology of the target organ toxicity. Poor solubility of the compounds at normal urinary pH was considered a possible mechanism for the crystalluria.
 ...
PMID:Urinary tract toxicity in rats following administration of beta 3-adrenoceptor agonists. 1020 80

The purpose of the present investigation is to reveal the specifics of the nutrition, nutritional behavior (habits), the prevalence of obesity and of certain chronic diseases among workers. The subjects were 264 workers (203 males and 61 females) from the ammonium production department of a fertilizer plant, divided into two age groups: under and over 30 years of age. The data were collected by means of a food-frequency questionnaire about daily nutrition and the average quantity of food. The nutritional status was assessed on the basis of BMI. All workers underwent clinical examinations conducted by a range of different experts, including an internal diseases specialist, a neurologist, a cardiologist, an opthalmologist, an otorhino-laryngologist, and a dermatologist. Twenty hematological and biochemical indicators in blood and serum were measured. Assessment of the individual energy intake showed that hyperenergetic nutrition was typical of 67% of workers because of extra intake of fat, which was seen in 87.9% of all individuals examined. The daily fat intake of over 40E% was typical for almost half the females (45.9%). All age and gender groups displayed hyperprotein nutrition with pronounced cellulose (fiber) deficit and a high daily sodium intake. The frequency of overweight individuals (BMI = 25, 1-30 kg/m2) was 43.9%, whereas that of obese individuals (BMI = > 30 kg/m2) was 23.1%. A total of 67% of workers had excessive body mass. The hypertension prevalence rose significantly from 6.9% in Group I to 34.5% in Group II, and to 57.4% in Group III. Coronary heart disease was rare, but the seven cases registered were among the overweight workers. The radiculitis prevalence among workers with normal body mass was two-fold lower in comparison with both groups (overweight and obesity). We conclude that hyperenergetic and unbalanced nutrition is a factor that determines the prevalence of overweight and obesity. A significantly higher percent of overweight and obese workers suffered from hypertension, liver disease, diabetes, coronary heart disease, and eye-vessel diseases. A tendency toward rising radiculitis and musculoskeleton system disease prevalence was seen that parallels the increase in BMI.
 ...
PMID:Nutrition, nutritional habits, obesity, and prevalence of chronic diseases in workers. 1037 17

Key enzymes of the glyoxylate cycle (isocitrate lyase and malate synthetase) were found in the liver and kidney of rats suffering from alloxan diabetes. The activities of these enzymes in the liver were 0.080 and 0.0430 U/mg protein, respectively. Isocitrate lyase activity in the kidney was 0.030 U/mg protein, and that of the malate synthetase was 0.018 U/mg protein. Peroxisomal localization of the enzymes was shown. A novel malate dehydrogenase isoform was found in a liver of rats suffering from the alloxan diabetes. The isocitrate lyase was isolated by selective (NH4)2SO4 precipitation and DEAE-Toyopearl chromatography. The resulting enzyme preparation had specific activity 6.1 U/mg protein, corresponding to 76.25-fold purification with 32.6% yield. The isocitrate lyase was found to follow the Michaelis--Menten kinetic scheme (Km for isocitrate, 0.08 mM) and to be competitively inhibited by glucose 1-phosphate (Ki = 1. 25 mM), succinate (Ki = 1.75 mM), and citrate (Ki = 1.0 mM); the pH optimum of the enzyme was 7.5 in Tris-HCl buffer.
 ...
PMID:Subcellular localization and properties of glyoxylate cycle enzymes in the liver of rats with alloxan diabetes. 1052 15

Human plasma contains inhibitors, which control the activity of proteolytic enzymes. Alpha-1-proteinase inhibitor and alpha-2-macroglobulin are two of them present in high concentration in human plasma, which inhibit action of trypsin among other proteinases. The trypsin inhibitory capacity (TIC) of human plasma is observed to be decreased in pathological conditions like diabetes mellitus. The mechanisms of decrease in TIC was due to nonenzymatic glycosylation of alpha-1-proteinase inhibitor (A1PI). A1PI was partially purified from normal human plasma by steps involving ammonium sulphate precipitation, DEAE Sepharose CL6B chromatography, Concanavalin A Sepharose Chromatography and Sephadex G-100 Gel filtration. Purified inhibitor was glycosylated in vitro by incubating it with varying glucose concentrations, under nitrogen for different periods of time in reducing conditions. After glycosylation, the molecular weight of inhibitor increased from 52 kDa to 57 KDa because of binding with glucose molecules. The percent free amino groups in the protein decreased with increasing glucose concentration and days of incubation. The TIC of such modified inhibitor decreased significantly. Decrease in TIC was dependent on the glucose concentration and period of incubation used during in-vitro glycosylation of native inhibitor.
 ...
PMID:Non enzymatic glycosylation of alpha-1-proteinase inhibitor of human plasma. 1070 66

Glutamate dehydrogenase (GDH) is allosterically activated by the amino acid leucine to mediate protein stimulation of insulin secretion. Children with the hyperinsulinism/hyperammonemia (HI/HA) syndrome have symptomatic hypoglycemia plus persistent elevations of plasma ammonium. We have reported that HI/HA may be caused by dominant mutations of GDH that lie in a unique allosteric domain that is encoded within GDH exons 11 and 12. To examine the frequency of mutations in this domain, we screened genomic DNA from 48 unrelated cases with the HI/HA syndrome for exon 11 and 12 mutations in GDH. Twenty-five (52%) had mutations in these exons; 74% of the mutations were sporadic. Clinical manifestations included normal birth weight, late onset of hypoglycemia, diazoxide responsiveness, and protein-sensitive hypoglycemia. Enzymatic studies of lymphoblast GDH in seven of the mutations showed that all had reduced sensitivity to inhibition with GTP, consistent with an increase in enzyme activity. Mutations had little or no effect on enzyme responses to positive allosteric effectors, such as ADP or leucine. Based on the three-dimensional structure of GDH, the mutations may function by impairing the binding of an inhibitory GTP to a domain responsible for the allosteric and cooperativity properties of GDH.
Diabetes 2000 Apr
PMID:Molecular basis and characterization of the hyperinsulinism/hyperammonemia syndrome: predominance of mutations in exons 11 and 12 of the glutamate dehydrogenase gene. HI/HA Contributing Investigators. 1087 Dec 7

The chemistry of vanadium compounds that can be taken orally is very timely since a vanadium(IV) compound, KP-102, is currently in clinical trials in humans, and the fact that human studies with inorganic salts have recently been reported. VO(acac)2 and VO(Et-acac)2 (where acac is acetylacetonato and Et-acac is 3-ethyl-2,4-pentanedionato) have long-term in vivo insulin mimetic effects in streptozotocin induced diabetic Wistar rats. Structural characterization of VO(acac)2 and two derivatives, VO(Me-acac)2 and VO(Et-acac)2, in the solid state and solution have begun to delineate the size limits of the insulin-like active species. Oral ammonium dipicolinatooxovanadium(V) is a clinically useful hypoglycemic agent in cats with naturally occurring diabetes mellitus. This compound is particularly interesting since it represents the first time that a well-characterized organic vanadium compound with the vanadium in oxidation state five has been found to be an orally effective hypoglycemic agent in animals.
 ...
PMID:Chemistry and insulin-like properties of vanadium(IV) and vanadium(V) compounds. 1088 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>