UNIPROT:P01275 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P01275 (glucagon)
26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate whether glucagon affects the xylitol-induced increase in the production of purine bases (hypoxanthine, xanthine, and uric acid), the present study was performed with five healthy subjects. Intravenous administration of 300 mL 10% xylitol increased the plasma concentration and urinary excretion of purine bases, erythrocyte concentrations of adenosine monophosphate (AMP) and adenosine diphosphate (ADP), and blood concentrations of glyceraldehyde-3-phosphate (GA3P) + dihydroxyacetone phosphate (DHAP), fructose-1,6-bisphosphate (FBP), and lactic acid; it decreased the blood concentration of pyruvic acid and the plasma concentration and urinary excretion of inorganic phosphate. However, intravenous administration of 1 mg glucagon together with xylitol reduced the xylitol-induced changes in oxypurines, pyruvic acid, GABP + DHAP, and FBP, whereas it promoted the xylitol-induced increase in the urinary excretion of total purine bases and did not affect the xylitol-induced increase in the plasma concentration of total purine bases. In addition, in vitro study demonstrated that sodium pyruvate prevented the xylitol-induced degradation of adenine nucleotides in erythrocytes. These results suggested that gluconeogenesis due to glucagon increased the production of pyruvic acid, accelerated the conversion of NADH to NAD, and thereby prevented both the xylitol-induced degradation of adenine nucleotides in organs similar to erythrocytes and the inhibition of xanthine dehydrogenase in the liver and small intestine, resulting in decreases in the plasma concentration and urinary excretion of oxypurines. However, it was also suggested that in the liver storing glycogen, glucagon-induced glycogenolysis accumulated sugar phosphates, resulting in purine degradation, since the xylitol-induced increase in the NADH/NAD ratio partially blocked glycolysis at the level of GABP dehydrogenase. Therefore, administration of glucagon together with xylitol may synergistically increase purine degradation more than xylitol alone, despite decreases in the plasma concentration and urinary excretion of oxypurines.
...
PMID:Effect of glucagon on the xylitol-induced increase in the plasma concentration and urinary excretion of purine bases. 893 39

The influence of Ca2+ on hepatic gluconeogenesis was measured in the isolated perfused rat liver at different cytosolic NAD(+)-NADH potentials. Lactate and pyruvate were the gluconeogenic substrates and the cytosolic NAD(+)-NADH potentials were changed by varying the lactate to pyruvate ratios from 0.01 to 100. The following results were obtained: a) gluconeogenesis from lactate plus pyruvate was not affected by Ca(2+)-free perfusion (no Ca2+ in the perfusion fluid combined with previous depletion of the intracellular pools); gluconeogenesis was also poorly dependent on the lactate to pyruvate ratios in the range of 0.1 to 100; only for a ratio equal to 0.01 was a significantly smaller gluconeogenic activity observed in comparison to the other ratios. b) In the presence of Ca2+, the increase in oxygen uptake caused by the infusion of lactate plus pyruvate at a ratio equal to 10 was the most pronounced one; in Ca(2+)-free perfusion the increase in oxygen uptake caused by lactate plus pyruvate infusion tended to be higher for all lactate to pyruvate ratios; the most pronounced difference was observed for lactate/pyruvate ratio equal to 1. c) In the presence of Ca2+ the effects of glucagon on gluconeogenesis showed a positive correlation with the lactate to pyruvate ratios; for a ratio equal to 0.01 no stimulation occurred, but in the 0.1 to 100 range stimulation increased progressively, producing a clear parabolic dependence between the effects of glucagon and the lactate to pyruvate ratio. d) In the absence of Ca2+ the relationship between the changes caused by glucagon in gluconeogenesis and the lactate to pyruvate ratio was substantially changed; the dependence curve was no longer parabolic but sigmoidal in shape with a plateau beginning at a lactate/pyruvate ratio equal to 1; there was inhibition at the lactate to pyruvate ratios of 0.01 and 0.1 and a constant stimulation starting with a ratio equal to 1; for the lactate to pyruvate ratios of 10 and 100, stimulation caused by glucagon was much smaller than that found when Ca2+ was present. e) The effects of glucagon on oxygen uptake in the presence of Ca2+ showed a parabolic relationship with the lactate to pyruvate ratios which was closely similar to that found in the case of gluconeogenesis; the only difference was that inhibition rather than stimulation of oxygen uptake was observed for a lactate to pyruvate ratio equal to 0.01; progressive stimulation was observed in the 0.1 to 100 range. f) In the absence of Ca2+ the effects of glucagon on oxygen uptake were different; the dependence curve was sigmoidal at the onset, with a well-defined maximum at a lactate to pyruvate ratio equal to 1; this maximum was followed by a steady decline at higher ratios; at the ratios of 0.01 and 0.1 inhibition took place; oxygen uptake stimulation caused by glucagon was generally lower in the absence of Ca2+ except when the lactate to pyruvate ratio was equal to 1. The results of the present study demonstrate that stimulation of gluconeogenesis by glucagon depends on Ca2+. However, Ca2+ is only effective in helping gluconeogenesis stimulation by glucagon at highly negative redox potentials of the cytosolic NAD(+)-NADH system. The triple interdependence of glucagon-Ca(2+)-NAD(+)-NADH redox potential reveals highly complex interrelations that can only be partially understood at the present stage of knowledge.
...
PMID:Ca2+ dependence of gluconeogenesis stimulation by glucagon at different cytosolic NAD(+)-NADH redox potentials. 936 5

In the present study, we examined the ability of adenosine 3',5'-cyclic monophosphate (cAMP) to reduce elevated levels of cytosolic Ca2+ concentration ([Ca2+]i) in pancreatic beta-cells. [Ca2+]i and reduced pyridine nucleotide, NAD(P)H, were measured in rat single beta-cells by fura 2 and autofluorescence microfluorometry. Sustained [Ca2+]i elevation, induced by high KCl (25 mM) at a basal glucose concentration (2.8 mM), was substantially reduced by cAMP-increasing agents, dibutyryl cAMP (DBcAMP, 5 mM), an adenylyl cyclase activator forskolin (10 microM), and an incretin glucagon-like peptide-1-(7-36) amide (10(-9) M), as well as by glucose (16.7 mM). The [Ca2+]i-reducing effects of cAMP were greater at elevated glucose (8.3-16.7 mM) than a basal glucose (2.8 mM). An inhibitor of protein kinase A (PKA), H-89, counteracted [Ca2+]i-reducing effects of cAMP but not those of glucose. Okadaic acid, a phosphatase inhibitor, at 10-100 nM also reduced sustained [Ca2+]i elevation in a concentration-dependent manner. Glucose, but not DBcAMP, increased NAD(P)H in beta-cells. [Ca2+]i-reducing effects of cAMP were inhibited by 0.3 microM thapsigargin, an inhibitor of the endoplasmic reticulum (ER) Ca2+ pump. In contrast, [Ca2+]i-reducing effects of cAMP were not altered by ryanodine, an ER Ca(2+)-release inhibitor, Na(+)-free conditions, or diazoxide, an ATP-sensitive K+ channel opener. In conclusion, the cAMP-PKA pathway reduces [Ca2+]i elevation by sequestering Ca2+ in thapsigargin-sensitive stores. This process does not involve, but is potentiated by, activation of beta-cell metabolism. Together with the known [Ca2+]i-increasing action of cAMP, our results reveal dual regulation of beta-cell [Ca2+]i by the cAMP-signaling pathway and by a physiological incretin.
...
PMID:[Ca2+]i-reducing action of cAMP in rat pancreatic beta-cells: involvement of thapsigargin-sensitive stores. 948 42

The ATP-analogue adenylyl(beta,gamma-methylene)diphosphonate was chosen as substrate for the cytochemical localization of adenylate cyclase (AC) activity. The tissues investigated covered normal rat liver and liver from carcinogen-treated animals with preneoplastic lesions and hepatocellular neoplasms, as well as cultured liver cells. The AC reaction product methylene diphosphonate was precipitated with Pb2+ immediately at the place of production. This approach permitted a precise localization of AC activity by light and electron microscopy. The specificity of the AC reaction was demonstrated by control reactions, including inhibition of AC with 2'5'-dideoxyadenosine and activation with forskolin, glucagon, and cholera toxin. Endogenous phosphatases were inhibited with tetramisole and NAD. In normal liver, AC activity was mainly localized in the sinusoidal membrane of hepatocytes. A distinct gradient in activity was observed within the liver lobule. Hepatocytes localized around the terminal hepatic venule showed a significant higher AC activity compared to hepatocytes near the portal tract. AC was clearly decreased in focal preneoplastic liver lesions of the glycogenotic-basophilic cell lineage leading to hepatocellular carcinomas. Cytochemically detected intensity of AC activity corresponded to data obtained by microbiochemical assays in laser-dissected tissue samples. A remarkable interdependence of AC activity and degree of differentiation was also seen in epithelial rat liver cell lines: Highly differentiated cells show high enzyme activity and vice versa, as shown by both cytochemical and biochemical examinations. It is concluded that alterations in cellular signal transduction caused by alterations in AC activity play an important role in hepatocarcinogenesis.
...
PMID:Cytochemical and biochemical studies on adenylate cyclase activity in preneoplastic and neoplastic liver tissue and cultured liver cells. 955 27

Stress mediators play a major role in inducing the hypermetabolic stress state in the liver after major injuries. The majority of studies on the effect of mediators on hepatocytes have focused on single factor effects or on the effect of very complex additives (e. g., serum), and there are no reports which have rigorously identified specific interactions between stress mediators. We used a factorial design experimental approach to evaluate the effects of a four to five day exposure to hormone (glucagon, hydrocortisone, and epinephrine) and cytokine [tumor necrosis factor-alpha (TNF-alpha) interleukin-1beta (IL-1beta) and interleukin-6 (IL-6)] stress mediators on stable cultures of rat hepatocytes. Both individual-factor effects and two factor interactions on the metabolism of urea, glucose, lactate, ketone bodies, albumin, and fibrinogen were evaluated. The cultured hepatocyte model exhibited physiologic responses to the applied stress mediators. While hydrocortisone and epinephrine had no effect, glucagon induced an increase in glucose and urea synthesis. Interleukin-6 increased fibrinogen and decreased albumin production. Furthermore, IL-6 and glucagon caused an increase in the ketone-body ratio (KBR = [acetoacetate]/[beta-hydroxybutyrate]), which is in equilibrium with the intramitochondrial NAD+/NADH. Tumor necrosis factor-alpha and IL-1beta, on the other hand, decreased the KBR. An important two-factor interaction between IL-1beta and IL-6 was identified, namely that IL-1beta effectively negates the positive effect of IL-6 on the KBR when both are present. These results provide further understanding of the effect of stress mediators on hepatic function and metabolism. These effects may have important implications in the pathogenesis of progressive organ dysfunction which often follows prolonged inflammatory states triggered by major injuries.
...
PMID:Metabolic effects of stress mediators on cultured hepatocytes. 1019 93

The early (min </= 1) and late (min 45) changes in NAD(P)H fluorescence caused by alpha-D-glucose pentaacetate, beta-L-glucose pentaacetate, and beta-D-galactose pentaacetate (1.7 mM each), alone or together with either L-leucine (10.0 mM) or D-glucose (8.3 mM), were monitored in purified pancreatic B and non-B rat islet cells. Whilst D-glucose caused a rapid increase in the NAD(P)H signal in B-cells, but not so in non-B cells, alpha-D-glucose pentaacetate, but not the two other monosaccharide esters, rapidly augmented the NAD(P)H signal in both B and non-B cells. After 45 min, the NAD(P)H signal was increased by either D-glucose in both B and non-B islet cells or alpha-D-glucose pentaacetate. At this late time, beta-L-glucose pentaacetate also increased the NAD(P)H signal in B cells exposed to L-leucine. These findings emphasize the relevance of differences in the time course of D-glucose uptake by B and non-B islet cells as a determinant of rapid changes in redox state. They also provide further support for the role of intracellular Ca(2+) regulating the activity of key Ca(2+)-responsive mitochondrial dehydrogenases. Last, they reinforce the view that the effects of hexose pentaacetates upon insulin and glucagon release entail a dual modality, linked either to the catabolism of their hexose moiety or to a direct effect of the esters themselves upon a stereospecific receptor system.
...
PMID:Differences in the time course of the metabolic response of B and non-B pancreatic islet cells to D-glucose and metabolized or non-metabolized hexose esters. 1046 77

The internal control of hepatocyte metabolism has been previously analysed using metabolic control analysis. The aim of this paper is to extend this analysis to include the responses of the cells to hormonal stimulus. Hepatocyte metabolism was divided into nine reaction blocks: glycogen breakdown, glucose release, glycolysis, lactate production, NADH oxidation, pyruvate oxidation, proton leak, mitochondrial phosphorylation and ATP consumption, linked by five intermediates: mitochondrial membrane potential, cytoplasmic NADH/NAD and total cellular ATP, glucose 6-phosphate and pyruvate. The kinetic responses of the reaction blocks to the intermediates were determined previously in the absence of added hormones. In this study, the changes in flux and intermediate levels that occurred upon addition of either glucagon or adrenaline were measured. From comparison of the fractional changes in fluxes and intermediate levels with the known kinetics of the system, it was possible to determine the primary sites of action of the hormones. The results show that the majority of processes in the cell are responsive to the hormones. The notable exception to this is the failure of adrenaline to have a direct effect on glycolysis. The activity change of each metabolic block observed in the presence of either hormone was quantified and compared to the indirect effects on each block caused by changes in metabolite levels. The second stage of the analysis was to use the calculated activity changes and the known control pattern of the system to give a semiquantitative analysis of the regulatory pathways employed by the hormones to achieve the changes in fluxes and metabolite levels. This was instructive in analysing, for example, how glucagon caused a decrease in flux through glycolysis and an increase in oxidative phosphorylation without large changes in metabolite levels (homeostasis). Conversely, it could be seen that the failure of adrenaline to maintain a constant glucose 6-phosphate concentration was due to the stimulation of glycogen breakdown and inhibition of glucose release.
...
PMID:The responses of rat hepatocytes to glucagon and adrenaline. Application of quantified elasticity analysis. 1051

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoprotein that utilizes NAD(P)H as an electron donor, catalyzing the two-electron reduction and detoxification of quinones and their derivatives. NQO1-/- mice deficient in NQO1 activity and protein were generated in our laboratory (Rajendirane, V., Joseph, P., Lee, Y. H., Kimura, S., Klein-Szanto, A. J. P., Gonzalez, F. J., and Jaiswal, A. K. (1998) J. Biol. Chem. 273, 7382-7389). Mice lacking a functional NQO1 gene (NQO1-/-) were born normal and reproduced adeptly as the wild-type NQO1+/+ mice. In the present report, we show that NQO1-/- mice exhibit significantly lower levels of abdominal adipose tissue as compared with the wild-type mice. The NQO1-/- mice showed lower blood levels of glucose, no change in insulin, and higher levels of triglycerides, beta-hydroxy butyrate, pyruvate, lactate, and glucagon as compared with wild-type mice. Insulin tolerance test demonstrated that the NQO1-/- mice are insulin resistant. The NQO1-/- mice livers also showed significantly higher levels of triglycerides, lactate, pyruvate, and glucose. The liver glycogen reserve was found decreased in NQO1-/- mice as compared with wild-type mice. The livers and kidneys from NQO1-/- mice also showed significantly lower levels of pyridine nucleotides but an increase in the reduced/oxidized NAD(P)H:NAD(P) ratio. These results suggested that loss of NQO1 activity alters the intracellular redox status by increasing the concentration of NAD(P)H. This leads to a reduction in pyridine nucleotide synthesis and reduced glucose and fatty acid metabolism. The alterations in metabolism due to redox changes result in a significant reduction in the amount of abdominal adipose tissue.
...
PMID:In vivo role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the regulation of intracellular redox state and accumulation of abdominal adipose tissue. 1130 86

Complete lack of transcription factor PDX-1 leads to pancreatic agenesis, whereas heterozygosity for PDX-1 mutations has been recently noted in some individuals with maturity-onset diabetes of the young (MODY) and in some individuals with type 2 diabetes. To determine how alterations in PDX-1 affect islet function, we examined insulin secretion and islet physiology in mice with one PDX-1 allele inactivated. PDX-1(+/-) mice had a normal fasting blood glucose and pancreatic insulin content but had impaired glucose tolerance and secreted less insulin during glucose tolerance testing. The expression of PDX-1 and glucose transporter 2 in islets from PDX-1(+/-) mice was reduced to 68 and 55%, respectively, whereas glucokinase expression was not significantly altered. NAD(P)H generation in response to glucose was reduced by 30% in PDX-1(+/-) mice. The in situ perfused pancreas of PDX-1(+/-) mice secreted about 45% less insulin when stimulated with 16.7 mm glucose. The K(m) for insulin release was similar in wild type and PDX-1(+/-) mice. Insulin secretion in response to 20 mm arginine was unchanged; the response to 10 nm glucagon-like peptide-1 was slightly increased. However, insulin secretory responses to 10 mm 2-ketoisocaproate and 20 mm KCl were significantly reduced (by 61 and 66%, respectively). These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets.
...
PMID:Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. 1178 23

1. The concentration and oxidoreduction state of the liver nicotinamide nucleotides of rats subjected to a number of hormonal treatments have been measured. 2. Adrenalectomy decreases the NADP(+) content by 80% but has little effect on NAD(+), NADH or NADPH. High doses of cortisone produce similar changes, but more physiological doses (5mug. daily) tend to increase the NADP(+) content. 3. Glucagon treatment of normal rats lowered the NADH and NADP(+) concentrations but did not affect the total amounts present. Growth hormone increased the concentrations and total amounts of NAD(+) and NADH but significantly decreased the concentrations and total amounts of NADP(+) and NADPH. 4. Measurements have been made of a number of enzymes in the livers of adrenalectomized and glucagon-treated rats that could affect the oxidoreduction state of NADP. The activities of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase are not affected by adrenalectomy or treatment with cortisone or glucagon. Nor does adrenalectomy affect the activity of NADPH-cytochrome c oxidoreductase or NADPH-glutathione oxidoreductase. The hepatic content of glutathione is, however, decreased 50% by adrenalectomy. 5. Measurements of the oxidation of [1-(14)C]glucose and [6-(14)C]glucose by liver slices from adrenalectomized rats showed that glucose oxidation was substantially normal, although phenazine methosulphate caused a smaller stimulation of the oxidation of C-1 of [1-(14)C]glucose in slices from the livers of adrenalectomized rats than it did with slices from controls. The hepatic synthesis of lipids from [1-(14)C]glucose was marginally increased in adrenalectomized rats. 6. The additional NADP(+) found when liver is extracted with 0.02n-sulphuric acid-0.1m-sodium sulphate is less affected than the NADP(+) extracted with 0.1n-hydrochloric acid in adrenalectomized or glucagon-treated rats. Hooded Norway rats appear to have less of this extra form of NADP(+) than albino rats. 7. An attempt has been made to correlate the observed changes in the nicotinamide nucleotides with metabolic patterns prevailing in different hormonal conditions.
...
PMID:THE EFFECT OF DIFFERENT HORMONAL CONDITIONS ON THE CONCENTRATION AND OXIDOREDUCTION STATE OF THE NICOTINAMIDE NUCLEOTIDES OF RAT LIVER. 1433 53

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