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

Normal rats fed for 105 days on an experimental diet made up of standard laboratory chow supplemented with 0.5% of a mixture of brominated sunflower-olive oil (BVO) developed a significant increase in the triacylglycerol content of the heart, liver and soleus muscle compared to controls. In addition, BVO-treated rats had a decrease in plasma levels of triacylglycerol and total and HDL cholesterol. Plasma fatty acid levels and plasma post-heparin lipolytic activities, such as H-TGL, LPL, T-TGL and MGH were similar to those of control animals fed the standard chow alone. Heart PDHa (active portion of pyruvate dehydrogenase) was dramatically decreased in the BVO-fed rats. A faster rate of spontaneous lipolysis was recorded in the isolated perfused preparation of hearts from the experimental animals. The addition of 10(-7) M of glucagon to the perfusate, however, revealed a lipolytic effect comparable to the one observed in the control rats. In summary, our findings of normal fatty acids and low triacylglycerol plasma levels associated with normal activities of the various PHLA (post-heparin lipolytic activity) enzymes suggest that accumulation of triacylglycerol in heart muscle may not be explained essentially in terms of an elevated uptake and/or increased delivery of plasma fatty acids or plasma triacylglycerol. A decreased in situ catabolism of tissue triacylglycerol also appears unlikely because the spontaneous as well as the glucagon induced lipolysis in the heart both were found to be unimpaired.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of brominated vegetable oils on heart lipid metabolism. 403 63

A simplified procedure was developed for isolation of intact, hormone-sensitive liver cells in a high and reproducible yield. These cells produce glucose from various precursors at rates comparable to those achieved in isolated perfused liver. Glucagon enhanced glucose synthesis from pyruvate, dihydroxyacetone, fructose, or xylitol more effectively at low than at high substrate concentration. At high pyruvate concentrations (>2 mM), glucagon or adenosine 3':5'-cyclic monophosphate (0.1 mM) exerts a curious inhibition of gluconeogenesis that can be reverted to stimulation on addition of ethanol. It is suggested that glucagon and cyclic AMP inhibit pyruvate dehydrogenase and thus limit the supply of reducing equivalents needed for glucose formation. Supporting evidence for hormonal control of pyruvate dehydrogenase in isolated liver cells is provided by the fact that glucagon decreases and insulin increases decarboxylation of [1-(14)C]pyruvate. Calcium salts (1.3 mM) enhance glucose formation from pyruvate but greatly enhance the inhibition exerted by the divalent cationophore, A23187. Inhibition by glucagon of glucose synthesis from pyruvate is additive with the effects of A23187 + Ca(++). However, with dihydroxyacetone as substrate, glucagon partially reverses the inhibition exerted by A23187 + Ca(++). The results are consistent with glucagon effecting an inhibition of pyruvate dehydrogenase and a stimulation of hexosediphosphatase activities.
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PMID:Regulation of glucose synthesis in hormone-sensitive isolated rat hepatocytes. 436 84

Vasopressin or alpha-adrenergic agents such as phenylephrine or adrenaline, but not glucagon, elicited an initial decrease in flux through pyruvate dehydrogenase assayed by 14CO2 production from [1-14C]pyruvate in perfused rat liver. This rapid decrease in 14CO2 production was maximal within 1-2 min of exposure, concomitant with a rise in effluent pyruvate concentration: a subsequent return towards initial values in both parameters was completed well before 5 min. This time course was superposed with Ca2+ efflux from perfused liver, maximal (at 116 nmol/min per g wet wt. of liver) at 1-2 min of exposure. The percentage of the active (dephospho) form of pyruvate dehydrogenase was not decreased at 2 min of exposure. The effect on flux through pyruvate dehydrogenase by phenylephrine was abolished by prazosine, phentolamine or phenoxybenzamine. Ionophore A23187 also caused a depression in 14CO2 production from [1-14C]pyruvate and a rise in effluent pyruvate concentration, but this effect was stable for longer times, and it was delayed when Ca2+ was omitted from the perfusion medium. Responses of phenylephrine and A23187 were not additive. The results demonstrate that under the experimental conditions employed in intact perfused liver, the mitochondrial multienzyme system of pyruvate dehydrogenase is sensitive to vasopressin, alpha-adrenergic agents and A23187. The similar time course in Ca2+ efflux may be indicative of the involvement of Ca2+ in mediating this effect.
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PMID:Decreased flux through pyruvate dehydrogenase during calcium ion movements induced by vasopressin, alpha-adrenergic agonists and the ionophore A23187 in perfused rat liver. 613 70

Addition of phenylephrine to isolated perfused rat liver is followed by an increased 14CO2 production from [1-14C]glutamate, [1-14C]glutamine, [U-14C]proline and [3-14C]pyruvate, but by a decreased 14CO2 production from [1-14C]pyruvate. Simultaneously, there is a considerable decrease in tissue content of 2-oxoglutarate, glutamate and citrate. Stimulation of 14CO2 production from [1-14C]glutamate is also observed in the presence of amino-oxyacetate, suggesting a stimulation of glutamate dehydrogenase and 2-oxoglutarate dehydrogenase fluxes by phenylephrine. Inhibition of pyruvate dehydrogenase flux by phenylephrine is due to an increased 2-oxoglutarate dehydroxygenase flux. Phenylephrine stimulates glutaminase flux and inhibits glutamine synthetase flux to a similar extent, resulting in an increased hepatic glutamine uptake. Whereas the effects of NH4+ ions and phenylephrine on glutaminase flux were additive, activation of glutaminase by glucagon was considerably diminished in the presence of phenylephrine. The reported effects are largely overcome by prazosin, indicating the involvement of alpha-adrenergic receptors in the action of phenylephrine. It is concluded that stimulation of gluconeogenesis from various amino acids by phenylephrine is due to an increased flux through glutamate dehydrogenase and the citric acid cycle.
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PMID:Effect of phenylephrine on glutamate and glutamine metabolism in isolated perfused rat liver. 614 74

A detailed study of the control of liver pyruvate dehydrogenase activity by various hormones was carried out with perfused liver and isolated hepatocytes. Vasopressin produced a significant increase in the enzyme activity in fed rats, and the time course and sensitivity of the response was similar to that of glycogen phosphorylase a. The enzyme from starved animals was resistant to hormonal activation. The possible factors involved in the above effects are discussed. Angiotensin and phenylephrine also increased pyruvate dehydrogenase activity, and the magnitude of the response was of the same order as that to vasopressin by the liver enzyme. The effects of these hormones on pyruvate dehydrogenase activity were critically dependent on extracellular Ca2+, thus suggesting a role for this ion in the mechanism of action of the hormones. Insulin did not appear to have a role in the control of the enzyme activity, as shown by its lack of effect on the enzyme. Glucagon, in contrast with previous reports, produced a rapid, transient and significant increase in pyruvate dehydrogenase activity. The physiological importance of the above effects is discussed.
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PMID:Hormonal control of pyruvate dehydrogenase activity in rat liver. 639 71

In isolated rat hepatocytes phenylephrine promotes a rapid increase in the amount of pyruvate dehydrogenase present in its active form (PDHa). This action is mediated by alpha 1-adrenergic receptors and is not observed in Ca2+-depleted hepatocytes. It is mimicked by the Ca2+ ionophore A23187. No changes in metabolites known to affect PDH activity are measured 3 min after addition of phenylephrine. Glucagon also increases PDHa, its action is additive to that of phenylephrine. The action of phenylephrine on PDHa could be explained by an increase in mitochondrial free Ca2+.
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PMID:Effect of phenylephrine on pyruvate dehydrogenase activity in rat hepatocytes and its interaction with insulin and glucagon. 640 71

Fatty acid synthesis and CO2 production were evaluated in hepatocytes from lean and obese Zucker rats in the presence of 3H2O, and several carbon precursors. The incorporation of 3H2O into fatty acids was greater in obese compared to lean rats in both the isolated hepatocyte and in vivo. The rates of incorporation of 3H2O into fatty acids and cholesterol in hepatocytes of both lean and obese rats were linear for 2 hr, in the absence or presence of 16.7 mM glucose. Rates of fatty acid synthesis were higher in the presence of 16.7 mM glucose compared to the absence of glucose in both lean and obese while rates of cholesterol synthesis were similar. The incorporation of 3H2O into fatty acids, but not into cholesterol, was correlated with increasing glucose concentration and was 2 to three-fold higher in hepatocytes of obese compared to lean rats in the presence of several carbon precursors. Differences in CO2 production between lean and obese rats suggested increased pentose phosphate shunt activity, decreased pyruvate dehydrogenase activity, and lower tricarboxylic acid cycle activity in obese rats. Fatty acid synthesis and CO2 production from 3H2O and [U-14C]glucose in hepatocytes of lean and obese rats was similarly elevated by insulin and depressed by glucagon at several concentrations, suggesting that hepatocytes of obese animals respond to these hormones. These data indicate that rates of hepatic fatty acid synthesis although higher in obese rats respond to modulation in a fashion which is similar to the response in lean rats. The present studies suggest that the oxidation of several carbon precursors in the tricarboxylic acid cycle is diminished in obese compared to lean rats, but pentose phosphate shunt activity is greater in the obese Zucker rats.
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PMID:Regulation of lipid synthesis in hepatocytes from lean and obese Zucker rats. 679 6

To determine the effect of insulin-dependent diabetes mellitus (IDDM) on rates and pathways of hepatic glycogen synthesis, as well as flux through hepatic pyruvate dehydrogenase, we used 13C-nuclear magnetic resonance spectroscopy to monitor the peak intensity of the C1 resonance of the glucosyl units of hepatic glycogen, in combination with acetaminophen to sample the hepatic UDP-glucose pool and phenylacetate to sample the hepatic glutamine pool, during a hyperglycemic-hyperinsulinemic clamp using [1-13C]-glucose. Five subjects with poorly controlled IDDM and six age-weight-matched control subjects were clamped at a mean plasma glucose concentration of approximately 9 mM and mean plasma insulin concentrations approximately 400 pM for 5 h. Rates of hepatic glycogen synthesis were similar in both groups (approximately 0.43 +/- 0.09 mumol/ml liver min). However, flux through the indirect pathway of glycogen synthesis (3 carbon units-->-->glycogen) was increased by approximately 50% (P < 0.05), whereas the relative contribution of pyruvate oxidation to TCA cycle flux was decreased by approximately 30% (P < 0.05) in the IDDM subjects compared to the control subjects. These studies demonstrate that patients with poorly controlled insulin-dependent diabetes mellitus have augmented hepatic gluconeogenesis and relative decreased rates of hepatic pyruvate oxidation. These abnormalities are not immediately reversed by normalizing intraportal concentrations of glucose, insulin, and glucagon and may contribute to postprandial hyperglycemia.
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PMID:13C-nuclear magnetic resonance spectroscopy studies of hepatic glucose metabolism in normal subjects and subjects with insulin-dependent diabetes mellitus. 798 93

Maintenance of plasma glucose concentrations within a narrow range despite wide fluctuations in the demand (e.g. vigorous exercise) and supply (e.g. large carbohydrate meals) of glucose results from coordination of factors that regulate glucose release into and removal from the circulation. On a moment-to-moment basis these processes are controlled mainly by insulin and glucagon, whose secretion is reciprocally influenced by the plasma glucose concentration. In the resting postabsorptive state, release of glucose from the liver (equally via glycogenolysis and gluconeogenesis) is the key regulated process. Glycogenolysis depends on the relative activities of glycogen synthase and phosphorylase, the latter being the more important. The activities of fructose-1,6-diphosphatase, phosphoenolpyruvate carboxylkinase and pyruvate dehydrogenase regulate gluconeogenesis, whose main precursors are lactate, glutamine and alanine. In the postprandial state, suppression of liver glucose output and stimulation of skeletal muscle glucose uptake are the most important factors. Glucose disposal by insulin-sensitive tissues is regulated initially at the transport step and the mainly by glycogen synthase, phosphofructokinase and pyruvate dehydrogenase. Hormonally induced changes in intracellular fructose 2,6-bisphosphate concentrations play a key role in muscle glycolytic flux and both glycolytic and gluconeogenic flux in the liver. Under stressful conditions (e.g. hypoglycaemia, trauma, vigorous exercise), increased secretion of other hormones such as adrenaline, cortisol and growth hormone, and increased activity of the sympathetic nervous system, come into play; their actions to increase hepatic glucose output and to suppress tissue glucose uptake are partly mediated by increases in tissue fatty acid oxidation. In diabetes, the most common disorder of glucose homeostasis, fasting hyperglycaemia, results primarily from excessive release of glucose by the liver due to increased gluconeogenesis; postprandial hyperglycaemia results from both impaired suppression of hepatic glucose release and impaired skeletal muscle glucose uptake. These abnormalities are usually due to the combination of impaired insulin secretion and tissue resistance to insulin, the causes of which remain to be determined.
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PMID:Control of glycaemia. 837 4

The purpose of the present study was to determine whether intracerebral interleukin (IL)-1 mediates the endotoxin [lipopolysaccharide (LPS)]-induced increase in glucose flux. To accomplish this goal, a specific receptor antagonist for IL-1 (IL-1ra) or artificial cerebrospinal fluid was infused into the lateral ventricle via an intracerebroventricular cannula before, and for 4 h after, the intravenous injection of LPS. Whole body glucose flux was measured in conscious unrestrained rats using [3-3H]glucose. LPS increased both the plasma glucose concentration and the rate of glucose production (95 and 80%, respectively). In contrast, intracerebroventricular infusion of IL-1ra (2 mg/kg + 2 mg-kg-1.h-1) attenuated by approximately 50% the LPS-induced changes in glucose metabolism. IL-1ra also blunted the increase in plasma catecholamines, but not the elevation in glucagon and corticosterone concentrations, observed after LPS. Intracerebroventricular infusion of IL-1ra greatly reduced the LPS-induced hyperlactacidemia but did not alter the increase in muscle pyruvate dehydrogenase activity. An intravenous infusion of a 10-fold greater dose of IL-1ra, however, did not antagonize the LPS-induced increase in glucose flux. These data indicate that a major portion of the stimulation of glucose flux, as well as the increase in plasma catecholamines in response to LPS, is mediated by IL-1 within the central nervous system.
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PMID:Central interleukin-1 partially mediates endotoxin-induced changes in glucose metabolism. 877 25


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