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 alkaline, heparin-releasable lipoprotein lipase (LPL) activity of isolated, perfused rat hearts was compared with the residual neutral lipase (NL) activity detectable in the post nuclear supernatant (PNS) from a tissue homogenate. Both enzyme activities were increased by serum, heparin and apolipoprotein CII, inhibited by high salt concentrations and by immunotitration with an anti-LPL gamma-globulin fraction. Protamine sulphate from saline liver inhibited LPL activity and the NL activity only in the absence of serum. Incubation of the PNS NL under classic conditions of hormonal stimulation (by phosphorylation) did not alter its activity and upon short-term preperfusion of the hearts with norepinephrine and glucagon also unchanged LPL and NL activities were measured. Our experiments are indicative of a possible similarity between vascular LPL and tissue NL and show that the lipase activities are not sensitive towards hormonal stimulation.
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PMID:Comparison of heparin-releasable lipase and tissue neutral lipase activity of rat heart. 667 39

To characterize the relative toxicity of different bile salts, isolated hepatocytes were incubated with different concentrations of one bile salt or with identical concentrations of different bile salts and their conjugates. Incubation lasted for 1 hr; samples were taken at intervals and studied for enzyme release, urea synthesis and stimulation by glucagon, and by electron microscopy. While the trihydroxylated bile salt, taurocholate, did not produce alterations at concentrations up to 1,500 microM, the dihydroxylated salts, chenodeoxy- and deoxycholate, caused enzyme release and membrane lysis, and inhibited urea synthesis at concentrations above 500 microM. In contrast, ursodeoxycholate was ineffective at concentrations up to 1,500 microM. Conjugation of these bile salts did not result in significant differences with the exception of deoxycholate conjugates which induced enzyme leakage more rapidly. Studies of lipid membrane vesicles revealed corresponding alterations. The monohydroxylated salt, taurolithocholate, caused cellular damage as indicated by enzyme loss and impairment of hormonal sensitivity of cells at low concentrations (30 to 100 microM). Dihydroxylated salts produced a different time course of membrane leakage, ultrastructural changes and release of volume marker and lipid in liposomes, suggesting a possible different mechanism of damage induced by this bile salt. Both systems can readily be used to study bile salt membrane interactions.
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PMID:Influence of hydroxylation and conjugation of bile salts on their membrane-damaging properties--studies on isolated hepatocytes and lipid membrane vesicles. 674 54

A great variety of peptide hormones have been demonstrated by immunocytochemical means in endocrine cells of the digestive system. Usually the specificity immunostaining in these cells is checked by antigen-adsorption of the antisera. This kind of specificity control, however, examines only antibody non-specificity but not staining non-specificity. Indeed staining non-specificities caused by ionic binding mechanisms are of considerable significance, at least for the immunostaining of some endocrine cell types (e.g. pancreatic glucagon- and PP-cells, pyloric gastrin-cells, intestinal GLI-cells). Therefore immunoreactivities of these cell types should be investigated under various experimental conditions. According to our present findings the following investigations should be performed to exclude staining non-specificities in immunostained endocrine cells of the digestive system: 1. Running of ascending dilutions of primary and secondary antisera. 2. Comparative investigations using crude antisera and purified antibodies against the peptide in question. 3. Use of phosphate buffered saline (PBS) with a relatively high salt content as a dilution agent for the antisera.
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PMID:[Specificity control in the immunohistochemistry of enteral peptide hormones]. 678 35

The effect of bile salts on RIAs of secretin, glucagon, insulin, and gastrin have been studied. Increasing concentrations of the sodium salts of taurocholic, glycochenodeoxycholic, taurochenodeoxycholic, glycocholic, and taurodeoxycholic acids progressively inhibit the binding of 125I-secretin to specific antibody, resulting in significant lowering of the B/F ratio at concentrations as low as 0.04 mM and almost complete inhibition at concentrations above 2.4 mM. The nonspecific inhibition by taurodeoxycholate results in a B/F vs. concentration curve resembling a secretion standard curve. The binding of 125I-secretin to charcoal is also inhibited by increasing concentrations of bile salts, although this effect is less marked than their effects on the immune reaction. The binding of 125I-glucagon, 125I-insulin, and 125I-gastrin to specific antisera is also inhibited by sodium taurocholate. Insulin binding is least affected. However, gastrin binding is inhibited by sodium taurocholate at a concentration as low as 0.2. The binding of 125I-insulin and 125I-gastrin to charcoal is also inhibited by sodium taurocholate. Thus bile salts interfere in the RIA of hormonal peptides by inhibiting both the immune reaction and the binding of labeled antigen to charcoal. These nonspecific effects must therefore be considered in RIA of body fluids containing high concentrations of bile salts. Treatment of plasma samples with anionic-binding resins can eliminate interference caused by high bile salt concentrations. However, these resins will also remove anionic hormonal peptides such as gastrin.
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PMID:The effects of bile salts on the radioimmunoassay of hormonal peptides. 704 May 70

The results of the study of the level of pancreatic hormones (insulin, glucagon, C-peptide and trypsin), carried out with the aim of finding out the character of relationship between hormonal disturbances and the state of carbohydrate metabolism, as well as the influence of oral rehydration therapy (ORT) with glucose-salt solutions on the function of the pancreas, are summarized. All subjects to be examined were divided into two groups receiving different kinds of ORT. The patients in group 1 (153 subjects) were treated with glucosolan and in group 2 (73 subjects), with sodium citrate in an amount of 2.5-5 lit. over the 6-hour period of treatment. The determination of the content of immunoreactive insulin, glucagon C-peptide and trypsin in the blood as the characteristics of the hormonal activity of the pancreas has made it possible to find out disturbances in the incretory and excretory activity of the pancreas in patients with acute enteric infections of different etiology. ORT with glucosolan and sodium citrate facilitates the restoration of pancreatic function in 65-70% of in patients with acute enteric infections of different etiology.
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PMID:[The effect of oral rehydration therapy on pancreatic function in patients with acute intestinal infections]. 777 84

Rat hepatocytes respond to glycogenolytic stimuli acting via phosphoinositide breakdown (e.g. alpha 1-adrenergic agonists, vasopressin) by oscillations of the free intracellular Ca2+ concentration ([Ca2+]i). We have investigated the action of metformin and phenformin, two anti-diabetic drugs of the biguanide type, on phenylephrine-induced [Ca2+]i oscillations. Metformin and phenformin lowered the frequency of the [Ca2+]i oscillations in a concentration-dependent manner with an IC50 of 0.1 mM and 1 microM, respectively. Simultaneous addition of the biguanides and insulin resulted in a further reduction of the frequency. By contrast, agents which increase the cellular cyclic AMP (cAMP) concentration (glucagon, forskolin, N,2'-O-dibutyryl-cAMP) reversed this inhibition. Furthermore, we investigated whether biguanides influenced the agonist-induced Ca2+ influx across the plasma membrane. When hepatocytes were loaded with the acetoxymethyl ester of fura-2 (fura-2/AM), addition of Mn2+ led to a quench of cellular fura-2, measured at the isosbestic excitation wavelength of 360 nm, until a new steady state was reached. Surprisingly, however, this addition of Mn2+ caused a marked increase of the fluorescence ratio simultaneously measured at 340 and 380 nm during the approach of the 360 nm signal to a new steady state. This observation can be understood on the basis of a compartmentalization of fura-2/AM into intracellular stores sensing the [Ca2+] therein. Subsequent application of phenylephrine resulted in a further decline of the fura-2 signal at 360 nm and a concomitant decrease of the fluorescence ratio. This second phase of the Mn2+ quench and the decrease of the fluorescence ratio could be diminished by addition of either 3 mM metformin or 30 microM phenformin. By contrast, when hepatocytes were loaded with fura-2/pentapotassium salt via a patch pipette, only the initial Mn(2+)-induced quench, measured at 360 nm, but no change of the fluorescence ratio, could be observed. The subsequent addition of phenylephrine and biguanides during the on-going quench caused no further changes, except for a fading oscillatory response. After loading hepatocytes with fluo-3 acetoxymethyl ester, the cells were permeabilized with 5 microM digitonin. Addition of inositol-1,4,5-trisphosphate (IP3) caused a rapid decrease of the remaining cellular fluorescence which could be effectively inhibited by 20 micrograms/ml heparin, indicating a release of Ca2+ from intracellular compartments mediated by IP3. This IP3-induced release of Ca2+ from intracellular stores could be diminished by prior addition of metformin and phenformin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Anti-diabetic biguanides inhibit hormone-induced intracellular Ca2+ concentration oscillations in rat hepatocytes. 799 93

Bile salt uptake by hepatocytes is modulated in part by changes in intracellular cyclic AMP. We studied the effect of activation of protein kinase C on cyclic AMP-mediated taurocholate uptake in isolated rat hepatocytes. Both dibutyryl cyclic AMP (2 x 10(-6) mol/L) and glucagon (10(-6) mol/L), which increase intracellular cyclic AMP, enhanced the initial uptake rate of taurocholate into hepatocytes, with maximal increases of 45% to 50% over the basal uptake rate. Vasopressin (10(-9) mol/L), a hormone known to activate protein kinase C, and phorbol-12,13-dibutyrate (10(-5) mol/L) significantly inhibited the glucagon-stimulated increase in taurocholate uptake rate (72% +/- 10% and 105% +/- 13% inhibition, respectively). Basal (unstimulated) taurocholate uptake rate was not affected by vasopressin or phorbol-12,13-dibutyrate. Down-regulation of the glucagon-stimulated transport was rapid and persisted during the 20-min experimental period. Angiotensin II had a similar but more transient inhibitory effect. Vasopressin and phorbol-12,13-dibutyrate suppression of glucagon-stimulated taurocholate uptake rate was not accompanied by diminished cyclic AMP levels. Moreover, vasopressin and phorbol-12,13-dibutyrate inhibited dibutyryl cyclic AMP-stimulated taurocholate uptake rate can be dissociated from alterations in the cyclic AMP levels.
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PMID:Vasopressin and phorbol-12,13-dibutyrate inhibit glucagon- or cyclic AMP-stimulated taurocholate uptake in isolated rat hepatocytes. 802 Aug 86

Although it has been firmly established that D-glucose inhibits glucagon secretion from pancreatic A cells, the regulatory mechanism of glucagon secretion by D-glucose has not been elucidated. To study this regulatory mechanism by D-glucose, the effects of hexoses and their derivatives on glucagon secretion from the A cells of isolated perfused rat pancreas were investigated. When these cells were perfused with D-glucose, D-fructose, D-sorbitol, D-galactose, 2-deoxy-D-glucose, D-gluconic acid sodium salt and D-glucosamine HCl salt, glucagon secretion was significantly inhibited. None of the hexoses or their derivatives tested were found to stimulate glucagon secretion. The effects of these sugars on glucagon secretion were independent of their metabolism in the cells. From the findings that the sugars both metabolized and unmetabolized in the cells demonstrated comparable inhibition of glucagon secretion from the isolated perfused rat pancreas, it is speculated that the recognition system for these sugars may be probably present on the A cell membrane and responsible for mediating these inhibitory effects of glucagon secretion.
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PMID:Effects of hexoses and their derivatives on glucagon secretion from isolated perfused rat pancreas. 807 3

Dicarboxylic acids have been proposed as an alternate lipid energetic substrate for total parenteral nutrition. No data are yet available on the possible effect of dicarboxylic acids on glucose metabolism in humans. Thus, we examined the effect of a continuous intravenous infusion of the sodium salt of the 10-carbon atom alyphatic dicarboxylic acid, sebacate (Sb), on insulin-dependent glucose metabolism in four control subjects, four patients with insulin-dependent diabetes mellitus, and four obese subjects. All subjects received a constant 5-hour infusion of saline or sebacate (6.6 g/h), in a randomized order on two different days. After 3 hours of infusion, a 120-minute euglycemic, hyperinsulinemic clamp procedure was performed (insulin infusion rate = 40 mU/m2 per minute). Glucose uptake, plasma sebacate, insulin, glucagon, C-peptide, and ketone bodies were measured. No significant differences in insulinemia were found among groups either during the saline infusion or the sebacate infusion. On the contrary, glucose uptake (molar) was significantly reduced during the sebacate vs the saline day in all three groups: 6.7 +/- 0.04 vs 3.7 +/- 1.3 in control subjects (p < .001), 4.6 +/- 0.4 vs 2.5 +/- 1.2 in patients with insulin-dependent diabetes mellitus (p < .001), and 4.8 +/- 0.5 vs 2.7 +/- 0.2 mg/kg per minute in obese subjects (p < .001). In conclusion, Sb administration was associated with a glucose-sparing effect as shown by the reduced glucose uptake in all patients studied. Sebacate did not stimulate insulin secretion, inasmuch as no modification of C-peptide plasma levels was observed after 3 hours of Sb infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dicarboxylic acids and glucose utilization in humans: effect of sebacate. 816 96

Lithium is the best available marker of proximal tubular reabsorption of fluid. The first part of the present thesis reviews the background for the use of the lithium clearance (CLi) method. Micropuncture studies on proximal reabsorption of lithium, showed that CLi is a reasonably correct measure of end-proximal fluid delivery rate, even during osmotic diuresis. During severe salt restriction, distal reabsorption of lithium renders the CLi method inappropriate in animals, but this problem does probably not occur in humans. The major current issue is whether a quantitatively significant reabsorption of lithium occurs in the loop of Henle. Available evidence is in accord with the interpretation that it does not occur. The interpretation of results form CLi studies depends to a surprising degree on the investigators beliefs about renal physiology. In the evaluation of proximal tubular function, the relevant parameter is the absolute proximal reabsorption rate of fluid and sodium. In the evaluation of integrated distal tubular reabsorption of sodium, the relevant parameter is the fractional distal reabsorption rate of sodium. The fractional CLi does not give meaningful information, and calculated absolute distal reabsorption rate of sodium is inherently not suited to detect modest changes in distal reabsorption leading to large changes in sodium excretion. Results from the use of the CLi method in relation to diabetes are reviewed in the second section. Even in IDDM patients with early diabetic nephropathy, the proximal reabsorption rate is elevated, resulting in a normal CLi despite glomerular hyperfiltration. Overnight euglycemia did not change GFR in IDDM patients, but during maintained euglycemia, GFR was normalized. A few hours of hyperglycemia prevented the decline in GFR, whereas CLi was unchanged. Thus hyperglycemia produced changes in renal function similar to those observed previously, but the time-course of the effect of euglycemia on kidney function is delayed. Plasma levels of atrial natriuretic peptide, renin and glucagon were not importantly affected by plasma glucose. In NIDDM patients CLi was normal, despite slight hyperfiltration, although this observation must be confirmed in a study with larger sample size. Prompted by the clinical observation of a marked decline in the GFR induced by carbonic anhydrase inhibitors, we studied the renal effects of acetazolamide in a controlled study.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lithium clearance in the evaluation of segmental renal tubular reabsorption of sodium and water in diabetes mellitus. 818 64


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