Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An effect of insulin on adipose-tissue adenosine 3':5'-cyclic monophosphate phosphodiesterase.

ABSTRACT: 1. 3':5'-Cyclic nucleotide phosphodiesterase activity was measured in homogenates prepared from epididymal fat-pads and isolated fat-cells incubated in the absence and presence of insulin. 2. Homogenates of insulin-treated tissues showed an increase in phosphodiesterase activity compared with controls. No effect of insulin was observed when the hormone was added directly to homogenates. 3. There was kinetic evidence for the presence of two 3':5'-cyclic nucleotide phosphodiesterases in adipose tissue. Insulin raised the maximal velocity of the low-K(m) enzyme and lowered the K(m) of the higher-K(m) enzyme. 4. It is suggested that the effect of insulin on adipose tissue phosphodiesterase accounts for the ability of this hormone to lower cyclic-AMP concentration in the tissue.

SUBMITTER: Loten EG

PROVIDER: S-EPMC1179583 | biostudies-other | 1970 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

The role of adenosine 3':5'-cyclic monophosphate in the regulation of insulin release. Properties of islet-cell adenosine 3':5'-cyclic monophosphate phosphodiesterase.

Project description:1. An assay has been developed with sufficient sensitivity for determination of the adenosine 3':5'-cyclic monophosphate diesterase activity in islets of Langerhans, and has been used to investigate the response of the enzyme to various agents which are known to affect insulin release. 2. The subcellular distribution of the enzyme in islets of Langerhans prepared from guinea-pig pancreas was investigated and over 70% of the activity present in the original homogenate was recovered in the supernatant fraction. 3. Gel filtration of the activity present in the supernatant fraction on Sephadex G-200 gave a single peak of activity with an apparent molecular weight of 200000. The phosphodiesterase activity in the peak fraction showed two apparent K(m) values for adenosine 3':5'-cyclic monophosphate (cyclic AMP) of 3mum and 30mum, suggesting the presence of two activities. The pH optimum of the activity with the low K(m) value was 8.7. 4. Theophylline, caffeine, 3-isobutyl-1-methylxanthine (SC-2964), glibenclamide, tolbutamide, xylitol and leucine were inhibitors of the activity with the low K(m) value; imidazole and arginine stimulated the activity, and glucose and diazoxide were without significant effect. 5. It is suggested that the agents theophylline, caffeine, SC-2964, glibenclamide, tolbutamide, leucine and imidazole may alter the intracellular concentration of cyclic AMP in islets of Langerhans by affecting the cyclic AMP phosphodiesterase activity in islet cells and in this way may affect insulin release.

| S-EPMC1174240 | biostudies-other

The effect of glucose, insulin and noradrenaline on lipolysis, and on the concentrations of adenosine 3':5'-cyclic monophosphate and adenosine 5'-triphosphate in adipose tissue.

Project description:Glycerol release and tissue concentrations of ATP and cyclic AMP were followed during the incubation of adipose tissue with or without glucose, insulin and noradrenaline. Glucose plus insulin or, to a lesser extent, glucose alone increased the accumulation of glycerol during incubations both with and without noradrenaline by slowing the decline in the rate of glycerol release with time. Insulin alone decreased the accumulation by accelerating the fall in glycerol release. In the absence of noradrenaline, ATP and cyclic AMP concentrations were not significantly affected by insulin or glucose. With noradrenaline or noradrenaline plus insulin the ATP concentration gradually fell. With noradrenaline plus glucose the ATP concentration fell rapidly and then stabilized, or, if insulin was also present, returned to the control value. In the presence of noradrenaline, the concentration of cyclic AMP rose during the first 20min and then fell. Insulin lowered the peak concentration of cyclic AMP, but glucose had no effect either on the peak value or the fall in the concentration of the nucleotide. The increase and fall in the concentration of cyclic AMP with noradrenaline or noradrenaline plus insulin bore similarities to the increase and decline in the lipolytic rate in incubations without glucose. It is proposed that glucose stimulates ATP production by furnishing glycerol 1-phosphate and thus removing free fatty acids, but that it can influence lipolysis by a mechanism which is distinct from any which is mediated by free fatty acids, possibly by inhibiting the inactivation of the lipase.

| S-EPMC1177561 | biostudies-other

Cyclic guanosine monophosphate signaling and phosphodiesterase-5 inhibitors in cardioprotection.

Project description:Cyclic guanosine monophosphate (cGMP) is an important intracellular second messenger that mediates multiple tissue and cellular responses. The cGMP pathway is a key element in the pathophysiology of the heart and its modulation by drugs such as phosphodiesterase (PDE)-5 inhibitors and guanylate cyclase activators may represent a promising therapeutic approach for acute myocardial infarction, cardiac hypertrophy, heart failure, and doxorubicin cardiotoxicity in patients. In addition, PDE-5 inhibitors may prove to be innovative therapeutic agents for enhancing the chemosensitivity of doxorubicin while providing concurrent cardiac benefit.

| S-EPMC4230443 | biostudies-literature

Gene expression in undifferentiated or cyclic adenosine monophosphate-exposed BeWo trophoblast cells

Project description:BeWo trophoblast cells differentiate in response to expsure to cyclic adenosine monophosphate (cAMP) analogs. Differentiation includes syncytialization (fusion) and hormonogenesis. The goal of this study was to globally determine transcripts differentially expressed in BeWo trophoblast cells following a 24-h exposure to 250 uM 8-bromo-cAMP.

2015-08-01 | GSE66840 | GEO

"cAMP sponge": a buffer for cyclic adenosine 3', 5'-monophosphate.

Project description:BackgroundWhile intracellular buffers are widely used to study calcium signaling, no such tool exists for the other major second messenger, cyclic AMP (cAMP).Methods/principal findingsHere we describe a genetically encoded buffer for cAMP based on the high-affinity cAMP-binding carboxy-terminus of the regulatory subunit RIbeta of protein kinase A (PKA). Addition of targeting sequences permitted localization of this fragment to the extra-nuclear compartment, while tagging with mCherry allowed quantification of its expression at the single cell level. This construct (named "cAMP sponge") was shown to selectively bind cAMP in vitro. Its expression significantly suppressed agonist-induced cAMP signals and the downstream activation of PKA within the cytosol as measured by FRET-based sensors in single living cells. Point mutations in the cAMP-binding domains of the construct rendered the chimera unable to bind cAMP in vitro or in situ. Cyclic AMP sponge was fruitfully applied to examine feedback regulation of gap junction-mediated transfer of cAMP in epithelial cell couplets.ConclusionsThis newest member of the cAMP toolbox has the potential to reveal unique biological functions of cAMP, including insight into the functional significance of compartmentalized signaling events.

| S-EPMC2766031 | biostudies-literature

Gene expression in undifferentiated or cyclic adenosine monophosphate-exposed BeWo trophoblast cells

2015-08-01 | E-GEOD-66840 | biostudies-arrayexpress

Hepatitis B Virus Evasion From Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase Sensing in Human Hepatocytes.

Project description:Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver disease and cancer worldwide. The mechanisms of viral genome sensing and the evasion of innate immune responses by HBV infection are still poorly understood. Recently, the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) was identified as a DNA sensor. In this study, we investigated the functional role of cGAS in sensing HBV infection and elucidate the mechanisms of viral evasion. We performed functional studies including loss-of-function and gain-of-function experiments combined with cGAS effector gene expression profiling in an infectious cell culture model, primary human hepatocytes, and HBV-infected human liver chimeric mice. Here, we show that cGAS is expressed in the human liver, primary human hepatocytes, and human liver chimeric mice. While naked relaxed-circular HBV DNA is sensed in a cGAS-dependent manner in hepatoma cell lines and primary human hepatocytes, host cell recognition of viral nucleic acids is abolished during HBV infection, suggesting escape from sensing, likely during packaging of the genome into the viral capsid. While the hepatocyte cGAS pathway is functionally active, as shown by reduction of viral covalently closed circular DNA levels in gain-of-function studies, HBV infection suppressed cGAS expression and function in cell culture models and humanized mice. Conclusion: HBV exploits multiple strategies to evade sensing and antiviral activity of cGAS and its effector pathways.

| S-EPMC6195855 | biostudies-literature

Dual specificity and novel structural folding of yeast phosphodiesterase-1 for hydrolysis of second messengers cyclic adenosine and guanosine 3',5'-monophosphate.

Project description:Cyclic nucleotide phosphodiesterases (PDEs) decompose second messengers cAMP and cGMP that play critical roles in many physiological processes. PDE1 of Saccharomyces cerevisiae has been subcloned and expressed in Escherichia coli. Recombinant yPDE1 has a KM of 110 ?M and a kcat of 16.9 s(-1) for cAMP and a KM of 105 ?M and a kcat of 11.8 s(-1) for cGMP. Thus, the specificity constant (kcat/KM(cAMP))/(kcat/KM(cGMP)) of 1.4 indicates a dual specificity of yPDE1 for hydrolysis of both cAMP and cGMP. The crystal structures of unliganded yPDE1 and its complex with GMP at 1.31 Å resolution reveal a new structural folding that is different from those of human PDEs but is partially similar to that of some other metalloenzymes such as metallo-?-lactamase. In spite of their different structures and divalent metals, yPDE1 and human PDEs may share a common mechanism for hydrolysis of cAMP and cGMP.

| S-EPMC4144708 | biostudies-literature

A DNA Aptamer for Cyclic Adenosine Monophosphate that Shows Adaptive Recognition.

Project description:As a ubiquitous second messenger, cyclic adenosine monophosphate (cAMP) mediates diverse biological processes such as cell growth, inflammation, and metabolism. The ability to probe these pathways would be significantly enhanced if we had a DNA-based sensor for cAMP. Herein, we describe a new, 31-base long single-stranded DNA aptamer for cAMP, denoted caDNApt-1, that was isolated by in vitro selection using systemic evolution of ligands after exponential enrichment (SELEX). caDNApt-1 has an approximately threefold higher affinity for cAMP than ATP, ADP, and AMP. Using non-denaturing gel electrophoresis and fluorescence spectroscopy, we characterized the structural changes caDNApt-1 undergoes upon binding to cAMP and revealed its potential as a cAMP sensor.

| S-EPMC6960355 | biostudies-literature

Fundamental reaction pathway and free energy profile for hydrolysis of intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP) catalyzed by phosphodiesterase-4.

Project description:As important drug targets for a variety of human diseases, cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes sharing a similar catalytic site. We have performed pseudobond first-principles quantum mechanical/molecular mechanical-free energy perturbation (QM/MM-FE) and QM/MM-Poisson-Boltzmann surface area (PBSA) calculations to uncover the detailed reaction mechanism for PDE4-catalyzed hydrolysis of adenosine 3',5'-cyclic monophosphate (cAMP). This is the first report on QM/MM reaction-coordinate calculations including the protein environment of any PDE-catalyzed reaction system, demonstrating a unique catalytic reaction mechanism. The QM/MM-FE and QM/MM-PBSA calculations revealed that the PDE4-catalyzed hydrolysis of cAMP consists of two reaction stages: cAMP hydrolysis (stage 1) and bridging hydroxide ion regeneration (stage 2). The stage 1 includes the binding of cAMP in the active site, nucleophilic attack of the bridging hydroxide ion on the phosphorus atom of cAMP, cleavage of O3'-P phosphoesteric bond of cAMP, protonation of the departing O3' atom, and dissociation of hydrolysis product (AMP). The stage 2 includes the binding of solvent water molecules with the metal ions in the active site and regeneration of the bridging hydroxide ion. The dissociation of the hydrolysis product is found to be rate-determining for the enzymatic reaction process. The calculated activation Gibbs free energy of ?16.0 and reaction free energy of -11.1 kcal/mol are in good agreement with the experimentally derived activation free energy of 16.6 kcal/mol and reaction free energy of -11.5 kcal/mol, suggesting that the catalytic mechanism obtained from this study is reliable and provides a solid base for future rational drug design.

| S-EPMC3209513 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data