Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic AMP plays a major, if not primary, role in the regulation of hepatic gluconeogenesis. The cyclic nucleotide acts on two levels. First, cAMP levels determine the phosphorylation state of key regulatory enzymes including pyruvate kinase and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Regulation of cAMP levels by glucagon, insulin, and catecholamines accounts in large part for minute-to-minute hormonal control of pathway flux in fed animals and during the transition from fed to starved; second, cAMP plays a key role in regulation of gene transcription of phosphoenolpyruvate carboxykinase, pyruvate kinase, glucokinase, and probably 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Cyclic AMP acts to induce synthesis of mRNA for phosphoenolpyruvate carboxykinase and probably fructose 1, 6-bisphosphatase while it suppresses transcription of the genes for pyruvate kinase and glucokinase. Its role in the regulation of gene transcription of the bifunctional enzyme and 6-phosphofructo 1-kinase remains to be defined. Insulin is the most important hormone for restraining the level of cAMP. Insulin acts to oppose the acute actions of cAMP on enzyme phosphorylation, presumably by activating a phosphodiesterase and thereby lowering cAMP levels. Insulin also opposes the action of hormones (alpha-adrenergic agonists, angiotensin, vasopressin) that act in liver via cAMP-independent phosphorylation. However, in the systems in which this has been studied, the cAMP-independent effects on gluconeogenic/glycolytic pathway flux are small in comparison to cAMP-dependent regulation. Insulin also opposes the action of cAMP on gene transcription by an as yet unknown mechanism. This effect does not appear to involve changes in the level of cAMP because the hormone also acts in cultured cells when added alone or in the presence of dexamethasone. The ability of insulin to lower hepatic cAMP levels and to modulate gene expression are important because restoration of acute regulatory hormone responsiveness to starved or diabetic animals could not occur if insulin were unable to lower cAMP levels and be the dominant factor in modulating the gene expression of these key regulatory enzymes. Clearly, the hepatic gluconeogenic/glycolytic pathway undergoes a complex but extremely well-integrated regulation by hormones that accounts in large part for the major role the organ plays in the control of glucose homeostasis.
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PMID:The role of cyclic AMP in rapid and long-term regulation of gluconeogenesis and glycolysis. 285 23

3-Mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase (PEPCK), decreased esterification of [1-14C] oleate and [1-14C] myristate in hepatocytes from fed rats. In the absence of 3-mercaptopicolinate, adrenaline, noradrenaline, vasopressin or angiotensin II increased esterification to triacylglycerol of [1-14C] oleate but not [1-14C] myristate. Cyclic AMP decreased esterification of both oleate and myristate. In the presence of 3-mercaptopicolinate, stimulation of oleate esterification by the catecholamines, vasopressin or angiotensin II was increased, and stimulatory effects of these hormones on myristate esterification were observed. Adrenaline, noradrenaline, vasopressin or angiotensin II increased 14CO2 production from both [1-14C] oleate and [1-14C] myristate but the degree of stimulation was similar in the absence or presence of 3-mercaptopicolinate. The results indicate a role for the catecholamines and angiotensin II in the regulation of liver fat metabolism and emphasize the potential importance of changes in activity of PEPCK as determinants of hepatic carbon flux.
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PMID:Hormonal regulation of fat esterification & oxidation in hepatocytes from fed rats: modulation by 3-mercaptopicolinate. 299 16

Adrenaline, noradrenaline, vasopressin and angiotensin increased 14CO2 production from [1-14C]oleate by hepatocytes from fed rats but not by hepatocytes from starved rats. The hormones did not increase 14CO2 production when hepatocytes from fed rats were depleted of glycogen in vitro. Increased 14CO2 production from ]1-14C]oleate in response to the hormones was observed when hepatocytes from starved rats were incubated with 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase. 3-Mercaptopicolinate inhibited uptake and esterification of [1-14C]oleate, slightly increased 14CO2 production from [1-14C]oleate and greatly increased the [3-hydroxybutyrate]/[acetoacetate] ratio. In the presence of 3-mercaptopicolinate 14CO2 production in response to the catecholamines was blocked by the alpha-antagonist phentolamine and required extracellular Ca2+. The effects of vasopressin and angiotensin were also Ca2+-dependent. The actions of the hormones of 14CO2 production from [I-14C]oleate by hepatocytes from starved rats in the presence of 3-mercaptopicolinate thus have the characteristics of the response to the hormones found with hepatocytes from fed rats incubated without 3-mercaptopicolinate. The stimulatory effects of the hormones on 14CO2 production from [1-14C]oleate were not the result of decreased esterification (as the hormones increased esterification) or increased beta-oxidation. It is suggested that the effect of the hormones to increase 14CO2 production from [1-14C]oleate are mediated by CA2+-activation of NAD+-linked isocitrate dehydrogenase, the 2-oxoglutarate dehydrogenase complex, and/or electron transport. The results also demonstrate that when the supply of oxaloacetate is limited it is utilized for gluconeogenesis rather than to maintain tricarboxylic acid-cycle flux.
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PMID:Stimulation of [1-14C]oleate oxidation to 14CO2 in isolated rat hepatocytes by the catecholamines, vasopressin and angiotensin. A possible mechanism of action. 640 2

A method is described for measuring rates of mitochondrial pyruvate carboxylation in hepatocytes treated with the polyene antibiotic, filipin, to render the plasma membrane permeable to substrates. With this approach it was possible to demonstrate that treatment of cells with glucagon or catecholamines results in a stimulation of mitochondrial CO2 fixation measured in situ comparable with that observed in the isolated mitochondria, in terms of time of onset of the response, hormone selectivity and sensitivity. In addition, angiotensin II and vasopressin were shown to enhance the activity of pyruvate carboxylase in both the intact mitochondria and filipin-treated cells, thus strengthening the postulate that this site is a major locus of hormone action in the control of gluconeogenesis. Addition of 3-mercaptopicolinic acid, to inhibit gluconeogenesis at the level of phosphoenolpyruvate carboxykinase, had no significant effect on the stimulation of pyruvate carboxylation by adrenaline, suggesting that the effect of the hormone at this site is independent of changes in activity of other enzymes further on in the pathway. The data presented preclude the possibility that acute effects of hormones on mitochondrial metabolism are solely artifacts of the preparation procedure.
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PMID:Hormonal stimulation of mitochondrial pyruvate carboxylation in filipin-treated hepatocytes. 641 Oct 66

Possible effects of adrenaline, noradrenaline, vasopressin, and angiotensin II to increase 14CO2 production from [1-14C]oleate were examined in hepatocytes from fed L-triiodothyronine (T3)-treated or control rats. Rates of 14CO2 production were decreased and rates of ketogenesis increased in hepatocytes from T3-treated rats. These changes were accompanied by a marked shift of the 3-hydroxybutyrate:acetoacetate concentration ratio towards acetoacetate. Rates of glucose and lactate release were decreased. Whereas the Ca2+-mobilizing hormones increased 14CO2 production from [1-14C]oleate by 64-84% with hepatocytes from control rats, they increased 14CO2 production from [1-14C]oleate by on 24-32% with hepatocytes from T3-treated rats. The magnitude of the response to the Ca2+-mobilizing hormones in hepatocytes from T3-treated rats was increased by the addition of 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, to the incubation medium (increases of 52-88%). In the presence of 3-mercaptopicolinate, the 3-hydroxybutyrate:acetoacetate concentration ratio in hepatocytes from fed, T3-treated rats was similar to that in hepatocytes from control rats in the absence of 3-mercaptopicolinate. The results demonstrate that hyperthyroidism per se does not lead to a loss of sensitivity, in terms of oleate oxidation, either to the catecholamines or to vasopressin and angiotensin II. The impaired ability of hepatocytes from T3-treated rats to respond to these hormones is a consequence of decreased net glycolytic flux or a more oxidized mitochondrial redox state.
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PMID:Effects of hyperthyroidism on stimulation of [1-14C]oleate oxidation to 14CO2 in isolated hepatocytes from fed rats by the catecholamines, vasopressin, and angiotensin II. 641 48