Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of a high content of acetic acid as mobile phase additive for the reversed-phase high-performance liquid chromatography (RP-HPLC) of several proteins and extracts of biological tissues was evaluated for a divinylbenzene (DVB)-based stationary phase, and the separations obtained with acetic acid gradients in acetonitrile, isopropanol or water were compared with classical polypeptide RP-HPLC on silica C4 with trifluoroacetic acid (TFA)-acetonitrile. The separation patterns for recombinant derived interleukin-1 beta (IL-1 beta) on the C4 column eluted with TFA-acetonitrile and the DVB column eluted with acetic acid-acetonitrile were similar, but only the polymeric column was able to separate the components present in an iodinated IL-1 beta preparation. Neither eluent had any harmful effect on the biological activity of IL-1 beta isolated after RP-HPLC. Several standard proteins could be separated when the polymeric column was eluted with acetic acid gradients in acetonitrile, isopropanol or water and, although the separation efficiency with acetic acid in water was lower than that in combination with classical organic modifiers, insulin, glucagon and human growth hormone (hGH) were eluted as sharp, symmetrical peaks. The recoveries of insulin and hGH were comparable for all three mobile phases (80-90%). The separation patterns obtained from a crude acetic acid extract of a normal and a diabetic, human pancreas analysed using acetic acid gradients with or without organic modifiers were found to be similar and comparable to those obtained on a silica C4 column eluted with an acetonitrile gradient in TFA. The principal differences resulted from the use of different UV wavelengths (215 nm for TFA-acetonitrile, 280 nm for acetic acid). Acetic acid extracts of recombinant derived hGH-producing Escherichia coli were separated on the DVB column eluted with an acetic acid gradient in water. Although the starting material was a highly complex mixture, the hGH isolated after this single-step purification was surprisingly pure (as judged by sodium dodecyl sulphate-polyacrylamide gel electrophoresis). Consequently several (pure) polypeptides and complex biological samples were separated on a polymeric stationary phase eluted with acetic acid gradients in water without the use of organic modifiers.
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PMID:Alternative mobile phases for the reversed-phase high-performance liquid chromatography of peptides and proteins. 205 Jul 79

Administration of isopropanol (1 ml/kg body weight) via the ip route significantly depressed the serum zinc concentration within 8 hr. A maximal increase in hepatic metallothionein was observed 16 hr after isopropanol. By 48 hr after treatment metallothionein levels in liver had returned to basal levels. The extent of metallothionein induction was comparable with that observed after ip administration of zinc. Plasma glucagon concentrations were significantly elevated 4 hr after isopropanol treatment. Adrenalectomy did not prevent the isopropanol-induced changes in serum zinc or hepatic metallothionein. This suggests a nonadrenal mechanism is responsible for the observed changes. To evaluate changes in metallothionein mRNA levels in liver, in vitro translation with the wheat germ system was used to evaluate translational activity. Analysis of the labeled metallothionein produced in vitro employed both covalent chromatography as well as SDS-polyacrylamide gel electrophoresis of carboxymethylated translation products. These methods suggested the maximum metallothionein mRNA level in total RNA extract occurred about 8 hr after administration of isopropanol. Similarly, when metallothionein mRNA levels were quantitated using dot blot hybridization to [32P]cDNA for mouse metallothionein I, maximum metallothionein mRNA appeared 8 hr after isopropanol administration. The overall response of these parameters in rats suggest that isopropanol administration leads to an inflammatory-like response that, with respect to zinc metabolism, has elements which are independent of the adrenal gland, but involve transcriptional regulation of the metallothionein gene in liver.
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PMID:Changes in rat liver metallothionein and metallothionein mRNA induced by isopropanol. 614 22

A competitive immunoassay for neuropeptide Y (NPY) based on capillary electrophoresis (CE) with laser-induced fluorescence detection was developed utilizing polyclonal antisera as the immunoreagent and fluorescein-labeled NPY as the tracer. The assay was performed with on-line mixing of reagents, automated injections, and a 3 s separation time. The assay had a detection limit of 850 pM. To detect NPY at lower concentrations, the assay was coupled on-line to reversed-phase capillary liquid chromatography (LC). In this arrangement, 5 microL samples were preconcentrated by capillary LC and eluted by a gradient of isopropanol-containing mobile phase. The resulting chromatographic peaks were monitored by the CE immunoassay. With preconcentration, the concentration detection limit was improved to 40 microM and NPY could be measured in push-pull perfusion samples collected from the paraventricular nucleus of freely moving rats. The technique was extended to simultaneous detection of NPY and glucagon secretion from islets of Langerhans.
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PMID:Capillary liquid chromatography of multiple peptides with on-line capillary electrophoresis immunoassay detection. 1169 3

The effect of different carbohydrate to protein ratios in food on cognitive functions and the relation between postprandial metabolic and cognitive changes were studied in 15 healthy male students. Subjects were tested in three sessions, separated by 1 week, for short-term changes in mood states, objective cognitive functions, blood parameters, and indirect calorimetry using a repeated-measures, counterbalanced cross-over design. Measurements were made after an overnight fast before and hourly during 3.5 h after test meal ingestion. The isoenergetic (1670 kJ) test meals consisted of three carbohydrate to protein ratios, i.e. a carbohydrate-rich (CHO[4:1]), balanced (BAL[1:1]), and protein-rich (PRO[1:4]) meal, respectively. Overall accuracy in short-term memory was best after the PRO[1:4] meal concomitant to the least variation in glucose metabolism and glucagon to insulin ratio (GIR). Related to changes in glucose metabolism and/or in the ratios of large neutral amino acids (LNAA), respectively, attention and decision times were transiently improved within the first hour after the CHO[4:1] meal, whereas after the first hour the BAL[1:1] and PRO[1:4] meal resulted in improved performance. Overall reaction times of a central task were fastest after the BAL[1:1] meal concomitant to the highest overall tyrosine (Tyr) to LNAA ratio. Our findings suggest that the carbohydrate to protein ratio in food specifically influences higher cognitive functions in the morning. Except for a transient positive effect of rising blood glucose after a carbohydrate-rich meal, a protein-rich or balanced meal seems to result in better overall cognitive performance presumably because of less variation in glucose metabolism and/or higher modulation in LNAA ratios indicated by the overall GIR.
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PMID:Carbohydrate to protein ratio in food and cognitive performance in the morning. 1189 69

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abarelix, ABX-EGF, ademetionine, agomelatine, AMGN-0007, 9-aminocamptothecin, AN-9, anecortave acetate, anidulafungin, AOD-9604, apolizumab, apomate, L-arginine hydrochloride, arzoxifene hydrochloride; Bevacizumab, BP-897, BufferGel; Capravirine, carboxyamidotriazole, carnosine, CC-4047, CEP-701, cerivastatin sodium, clofarabine, conivaptan hydrochloride, CP-461, CS-003; Daptomycin, darifenacin, decitabine, deferasirox, duloxetine hydrochloride; Eberconazole, Ecyd, efalizumab, eglumegad hydrate, EMD-72000, (-)-epigallocatechin gallate, exatecan mesilate, exenatide; Fampridine, fenretinide, ferumoxtran-10; Gadofosveset sodium, garenoxacin mesilate, genistein, glutamine, GPI-15715; Hexyl insulin M2, human insulin, HYB-165; Indisulam, irofulven; KRN-5500, L-796568, laurocapram, lidocaine/prilocaine, lonafarnib, lotrafiban; Melagatran, melatonin, 2-methoxyestradiol, metreleptin, motexafin gadoliniu, motexafin lutetium; Natalizumab, nelarabine, NO-aspirin, NSC-683864; ONO-6126; Pemetrexed disodium, pexelizumab, pirfenidone, PncCRM9, polyglutamate paclitaxel, pramlintide acetate pregabalin, PRO-2000; Ragaglitazar, ramelteon, rasagiline mesilate, rDNA insulin, recombinant glucagon-like peptide-1 (7-36) amide, recombinant human parathyroid hormone (1-84), reolysin RG228, roflumilast, roxifiban acetate, RPI-4610, rubitecan; Safinamide mesilate, solifenacin succinate, SRL-172; T-138067, tafenoquine succinate, tecadenoson, TER-286, tesaglitazar, tetrathiomolybdate, tezosentan disodium, TheraCIM, tigecycline, tipifarnib, tolvaptan, trabectedin, tributyrin, trimegestone, troxacitabine; UCN-01, urokinase alfa; Vinflunine, viscum fraxini 2; Xcellerated T cells, ximelagatran.
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PMID:Gateways to clinical trials. 1468 3

The hemodynamic effects of the glucagon-like peptide-1 (GLP-1) receptor agonist, exendin-4, and putative underlying mechanisms were assessed in conscious male Sprague-Dawley rats. At a dose of 25 ng kg(-1) i.v., exendin-4 had little effect, but doses of 250 and 2500 ng kg(-1) had significant tachycardic effects (+66 +/- 9 and +95 +/- 16 beats min(-1) at 5 min, respectively) and pressor actions (+10 +/- 2 and +12 +/- 1 mm Hg), accompanied by substantial falls in mesenteric vascular conductance (-38 +/- 3% and -47 +/- 3%) and increases in hindquarters vascular conductance (+82 +/- 14% and +126 +/- 15%). The latter were likely due to adrenaline-mediated activation of beta(2) adrenoceptors since they were abolished by the beta(2) adrenoceptor antagonist, ICI 118551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol) hydrochloride], or propranolol [(RS)-1-[(1-methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol], and absent in adrenal-demedullated rats. In the presence of beta-adrenoceptor antagonism, the tachycardic effects of exendin-4 were suppressed, but the pressor action was enhanced. Enhancement of the pressor action of exendin-4 was not seen in adrenal-demedullated rats or in animals given phentolamine in addition to propranolol, consistent with a component of the pressor action of exendin-4 being due to an adrenaline-mediated positive inotropic effect mediated by alpha-adrenoceptors. The mesenteric vasoconstrictor effect of exendin-4 was unaffected by antagonism of alpha-adrenoceptors, vasopressin receptors, angiotensin receptors, or GLP-1 receptors, although antagonism of the latter substantially inhibited the hindquarter vasodilator effects of exendin-4. These results are consistent with exendin-4 having cardiovascular effects through GLP-1 receptor-dependent and -independent mechanisms, some of which involve sympathoadrenal activation.
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PMID:Mesenteric vasoconstriction and hindquarters vasodilatation accompany the pressor actions of exendin-4 in conscious rats. 1622 40

During the last few years, reliable and simple tests have been proposed to estimate oxidative stress in vivo. Many of them can be easily adapted to automated analyzers, permitting the simultaneous processing of a large number of samples in a greatly reduced time, avoiding manual sample and reagent handling, and reducing variability sources. In this chapter, description of protocols for the estimation of reactive oxygen metabolites and the antioxidant capacity (respectively the d-ROMs and OXY Adsorbent Test, Diacron, Grosseto, Italy) by using the clinical chemistry analyzer SYNCHRON, CX 9 PRO (Beckman Coulter, Brea, CA, USA) is reported as an example of such an automated procedure that can be applied in the clinical setting. Furthermore, a calculation to compute a global oxidative stress index (Oxidative-INDEX), reflecting both oxidative and antioxidant counterparts, and, therefore, a potentially more powerful parameter, is also described.
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PMID:An easy and reliable automated method to estimate oxidative stress in the clinical setting. 1908 36

The infection caused by HIV leads to an activation of the immune system, which involves local and systemic oxidative stress. In HIV-positive (HIV+) patients, oxidative damage is the result of HIV infection and its progression through the replication of the virus. We have examined 52 subjects: 26 HIV+ patients, and 26 healthy subjects (NC). Analysis of the parameters of the oxidant/antioxidant status (total antioxidant capacity (TAC), hydroperoxides (free radicals, PRO), thiols as thiolic capacity, TC) was carried out by means of the OXY-Absorbent test, the d-Rom test, and the -SHp test, respectively. Healthy subjects presented the following values: TAC (micromol/ml) 259.5+/-40.5; TC (micromol/l) 434.09+/-18.31; PRO (mg/dl) 54.09+/-7.3; CD4+ cells (cells/ml) 850+/-333. Values of HIV+ patients were the following: TAC 218.73+/-18.55 (ns vs NC; TC 250.88+/-93.11 (p 0.001 vs NC); PRO 110.5+/-23.61 (p 0.0005 vs NC); CD4+ cells 354+/-323.35 (p 0.0005 vs NC). The statistical analysis shows a direct correlation between TAC vs CD4+ cells; an indirect correlation between hydroperoxides vs CD4+ cells; not significant result between thiolic capacity vs CD4+ cells; finally, good correlations between TAC, hydroperoxides, and thiolic capacity vs HIV-RNA. The data obtained have proven that HIV+ patients present a condition of important oxidative stress. We may affi rm that this disease concurs with an increase of extreme stress; a condition in which the antioxidant defences are present, but are insufficient in neutralising the damaging actions of reactive species of oxygen, thus contributing to an acceleration in the natural history of HIV infections.
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PMID:Oxidant/antioxidant status in patients with chronic HIV infection. 2039 80

An analysis of exhaled volatile organic compounds (VOC) may deliver systemic information quicker than available invasive techniques. Metabolic aberrations in pediatric type 1 diabetes (T1DM) are of high clinical importance and could be addressed via breathomics. Real-time breath analysis was combined with continuous glucose monitoring (CGM) and blood tests in children suffering from T1DM and age-matched healthy controls in a highly standardized setting. CGM and breath-resolved VOC analysis were performed every 5 minutes for 9 hours and blood was sampled at pre-defined time points. Per participant (n = 44) food intake and physical activity were identical and a total of 22 blood samples and 93 minutes of breath samples were investigated. The inter-individual variability of glucose, insulin, glucagon, leptin, and soluble leptin receptor relative to food intake differed distinctly between patients and controls. In T1DM patients, the exhaled amounts of acetone, 2-propanol, and pentanal correlated to glucose concentrations. Of note, the strength of these correlations strongly depended on the interval between food intake and breath sampling. Our data suggests that metabolic adaptation through postprandial hyperglycemia and related oxidative stress is immediately reflected in exhaled breath VOC concentrations. Clinical translations of our findings may enable point-of-care applicability of online breath analysis towards personalized medicine.
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PMID:Non-Invasive Assessment of Metabolic Adaptation in Paediatric Patients Suffering from Type 1 Diabetes Mellitus. 3171 11

Fasting duration has been associated with lower fasting blood glucose levels, but higher 2-hour post-load levels, and research has indicated an adverse effect of 'weekend behavior' on human metabolism. We investigated associations of fasting duration and weekday of examination with glucose, insulin, glucagon and incretin responses to an oral glucose tolerance test (OGTT). This cross-sectional study is based on data from the ADDITION-PRO study, where 2082 individuals attended a health examination including an OGTT. Linear regression analysis was applied to study the associations of overnight fasting duration and day of the week with glucose, insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) responses to an OGTT. We found that a one hour longer fasting duration was associated with 1.7% (95%CI:0.8,2.5) higher 2-hour glucose levels, as well as a 3.0% (95%CI:1.3,4.7) higher GIP and 2.3% (95%CI:0.3,4.4) higher GLP-1 response. Fasting insulin levels were 20.6% (95%CI:11.2,30.7) higher on Mondays compared to the other weekdays, with similar fasting glucose levels (1.7%, 95%CI:0.0,3.4). In this study longer overnight fasting duration was associated with a worsening of glucose tolerance and increased incretin response to oral glucose. We found higher fasting insulin levels on Mondays compared to the other days of the week, potentially indicating worsened glucose regulation after the weekend.
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PMID:Role of fasting duration and weekday in incretin and glucose regulation. 3216 18


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