scholarly journals The stimulation of glycogenolysis and gluconeogenesis in isolated hepatocytes by opioid peptides

1983 ◽  
Vol 216 (2) ◽  
pp. 507-510 ◽  
Author(s):  
E H Allan ◽  
I C Green ◽  
M A Titheradge
Keyword(s):  
Cyclic Amp ◽  
Opioid Peptides ◽  
Isolated Hepatocytes ◽  
Significant Inhibition ◽  
Leucine Enkephalin ◽  
Opioid Agonists ◽  
Independent Mechanism ◽  
Total Glucose ◽  
Glucose Output ◽  
Stimulation Of

The opioid agonists [leucine]enkephalin, [D-Ala2,D-Leu5]enkephalin and dynorphin-(1-13)-peptide, but not morphine, stimulated the conversion of [2-14C]pyruvate into glucose and glycogenolysis when added directly to isolated hepatocytes. Naloxone produced a small but significant inhibition of both the basal and stimulated rate of incorporation of label into glucose but had no effect on the total glucose output by the cells. The effects of the opioid peptides were mediated by a cyclic AMP-independent mechanism.

scholarly journals The stimulation of glycogenolysis in isolated hepatocytes by opioid peptides

1985 ◽  
Vol 227 (1) ◽  
pp. 191-197 ◽  
Author(s):  
R P Leach ◽  
E H Allan ◽  
M A Titheradge
Keyword(s):  
Opioid Peptides ◽  
Isolated Hepatocytes ◽  
Aminopeptidase Activity ◽  
Initial Product ◽  
Transient Nature ◽  
Adrenergic Antagonists ◽  
Lactate Formation ◽  
Glucose Output ◽  
Dependent Mechanism ◽  
Stimulation Of

Addition of the opioid peptides, [Leu]enkephalin and [Met]enkephalin, to isolated hepatocytes was shown to produce a stimulation of glycogenolysis comparable with that observed in the presence of maximal concentrations of glucagon, adrenaline or angiotensin. This stimulation was demonstrated to be the result of an activation of phosphorylase by a rapid Ca2+-dependent mechanism and was not decreased by the presence or either alpha- or beta-adrenergic antagonists, although it was dependent on the presence of the N-terminal tyrosine residue in the enkephalin molecule. It is suggested that this may be further evidence for specific opioid receptors in the liver. Addition of [Leu]enkephalin also inhibited lactate formation, indicating that the opioid peptides exert a concerted effect on hepatic carbohydrate metabolism to enhance glucose output. The transient nature of the effect of the enkephalins was shown to be the result of a rapid breakdown of the peptides in the incubation as a result of aminopeptidase activity, the initial product being the inactive des-tyrosine derivative.

scholarly journals The stimulation of glycogenolysis in isolated hepatocytes by opioid peptides

1986 ◽  
Vol 238 (2) ◽  
pp. 531-535 ◽  
Author(s):  
R P Leach ◽  
M A Titheradge
Keyword(s):  
Cyclic Amp ◽  
Opioid Peptides ◽  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Isolated Hepatocytes ◽  
Dependent Protein ◽  
Simultaneous Decrease ◽  
Glycogen Phosphorylase Activity ◽  
Stimulation Of

The opioid peptides [Leu]enkephalin and dynorphin-(1-13) were shown to enhance glycogen breakdown when added directly to hepatocytes. This was the result of a concerted effect on the enzymes of glycogen metabolism, with a stimulation of glycogen phosphorylase activity and a simultaneous decrease in glycogen synthase I activity. The latter only became significant when the enzyme was activated by incubating the cells in presence of 20 mM- or 40 mM-glucose. The effect of the opioid peptides was independent of an increase in cyclic AMP or any change in the activity ratio of the cyclic AMP-dependent protein kinase and was abolished by depleting the cells of Ca2+. Both [Leu]enkephalin and dynorphin-(1-13) produced a significant decrease in cyclic AMP formation, suggesting that in liver, as in neuronal tissue, they may act by inhibiting adenylate cyclase activity.

scholarly journals The ability of adenosine to decrease the concentration of fructose 2,6-bisphosphate in isolated hepatocytes. A cyclic AMP-mediated effect

1984 ◽  
Vol 218 (1) ◽  
pp. 157-163 ◽  
Author(s):  
R Bartrons ◽  
E Van Schaftingen ◽  
H G Hers
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Pyruvate Kinase ◽  
High Speed ◽  
Opposite Effect ◽  
Marked Decrease ◽  
Isolated Hepatocytes ◽  
Adenosine Transport ◽  
High Speed Supernatant ◽  
Stimulation Of

The presence of adenosine (25-250 microM) or of 2-chloroadenosine (2.5-100 microM) in the incubation medium caused a marked decrease in the concentration of fructose 2,6-bisphosphate in isolated hepatocytes. This effect was accompanied by an increase in the concentration of cyclic AMP, an activation of phosphorylase and of fructose 2,6-bisphosphatase, and an inactivation of pyruvate kinase and of 6-phosphofructo-2-kinase. As a rule, the changes in the fructose 2,6-bisphosphate-modifying system were slower but more persistent than those in the activities of phosphorylase and pyruvate kinase. The effect of the nucleoside to decrease the concentration of fructose 2,6-bisphosphate was not affected by an inhibitor of adenosine transport and could not be obtained in a liver high-speed supernatant. These data indicate that the effect of adenosine to decrease the concentration of fructose 2,6-bisphosphate is mediated by the stimulation of adenylate cyclase, secondary to the binding of adenosine to membranous receptors. Like glucagon, 2-chloroadenosine stimulated gluconeogenesis in isolated hepatocytes, whereas adenosine had an opposite effect.

scholarly journals Role of fructose 2,6-bisphosphate in the stimulation of glycolysis by anoxia in isolated hepatocytes

1982 ◽  
Vol 206 (2) ◽  
pp. 359-365 ◽  
Author(s):  
L Hue
Keyword(s):  
Skeletal Muscle ◽  
Cyclic Amp ◽  
Adenine Nucleotides ◽  
Lactate Production ◽  
Isolated Hepatocytes ◽  
Anaerobic Glycolysis ◽  
Anaerobic Conditions ◽  
Effect Of Glucose ◽  
Stimulation Of

1. Incubation of hepatocytes from fed or starved rats with increasing glucose concentrations caused a stimulation of lactate production, which was further increased under anaerobic conditions. 2. When glycolysis was stimulated by anoxia, [fructose 2,6-bis-phosphate] was decreased, indicating that this ester could not be responsible for the onset of anaerobic glycolysis. In addition, the effect of glucose in increasing [fructose 2,6-bisphosphate] under aerobic conditions was greatly impaired in anoxic hepatocytes. [Fructose 2,6-bisphosphate] was also diminished in ischaemic liver, skeletal muscle and heart. 3. The following changes in metabolite concentration were observed in anaerobic hepatocytes: AMP, ADP, lactate and L-glycerol 3-phosphate were increased; ATP, citrate and pyruvate were decreased: phosphoenolpyruvate and hexose 6-phosphates were little affected. Concentrations of adenine nucleotides were, however, little changed by anoxia when hepatocytes from fed rats were incubated with 50 mM-glucose. 4. The activity of ATP:fructose 6-phosphate 2-phosphotransferase was not affected by anoxia but decreased by cyclic AMP. 5. The role of fructose 2,6-bisphosphate in the regulation of glycolysis is discussed.

scholarly journals Stimulation of glycogenolysis by adenine nucleotides in the perfused rat liver

1986 ◽  
Vol 237 (3) ◽  
pp. 773-780 ◽  
Author(s):  
D B Buxton ◽  
S M Robertson ◽  
M S Olson
Keyword(s):  
Cyclic Amp ◽  
Adenine Nucleotides ◽  
Hepatic Metabolism ◽  
Hepatic Tissue ◽  
Adrenergic Stimulation ◽  
Portal Vein Pressure ◽  
Maximal Stimulation ◽  
Phenylephrine Infusion ◽  
Glucose Output ◽  
Stimulation Of

Infusion of adenine nucleotides and adenosine into perfused rat livers resulted in stimulation of hepatic glycogenolysis, transient increases in the effluent perfusate [3-hydroxybutyrate]/[acetoacetate] ratio, and increased portal vein pressure. In livers perfused with buffer containing 50 microM-Ca2+, transient efflux of Ca2+ was seen on stimulation of the liver with adenine nucleotides or adenosine. ADP was the most potent of the nucleotides, stimulating glucose output at concentrations as low as 0.15 microM, with half-maximal stimulation at approx. 1 microM, and ATP was slightly less potent, half-maximal stimulation requiring 4 microM-ATP. AMP and adenosine were much less effective, doses giving half-maximal stimulation being 40 and 20 microM respectively. Non-hydrolysed ATP analogues were much less effective than ATP in promoting changes in hepatic metabolism. ITP, GTP and GDP caused similar changes in hepatic metabolism to ATP, but were 10-20 times less potent than ATP. In livers perfused at low (7 microM) Ca2+, infusion of phenylephrine before ATP desensitized hepatic responses to ATP. Repeated infusions of ATP in such low-Ca2+-perfused livers caused homologous desensitization of ATP responses, and also desensitized subsequent Ca2+-dependent responses to phenylephrine. A short infusion of Ca2+ (1.25 mM) after phenylephrine infusion restored subsequent responses to ATP, indicating that, during perfusion with buffer containing 7 microM-Ca2+, ATP and phenylephrine deplete the same pool of intracellular Ca2+, which can be rapidly replenished in the presence of extracellular Ca2+. Measurement of cyclic AMP in freeze-clamped liver tissue demonstrated that adenosine (150 microM) significantly increased hepatic cyclic AMP, whereas ATP (15 microM) was without effect. It is concluded that ATP and ADP stimulate hepatic glycogenolysis via P2-purinergic receptors, through a Ca2+-dependent mechanism similar to that in alpha-adrenergic stimulation of hepatic tissue. However, adenosine stimulates glycogenolysis via P1-purinoreceptors and/or uptake into the cell, at least partially through a mechanism involving increase in cyclic AMP. Further, the hepatic response to adenine nucleotides may be significant in regulating hepatic glucose output in physiological and pathophysiological states.

scholarly journals Pancreastatin activates protein kinase C by stimulating the formation of 1,2-diacylglycerol in rat hepatocytes

1994 ◽  
Vol 303 (1) ◽  
pp. 51-54 ◽  
Author(s):  
V Sánchez-Margalet ◽  
M Lucas ◽  
R Goberna
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pertussis Toxin ◽  
Time Course ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Dependent Manner ◽  
Kinase C ◽  
Glucose Output ◽  
Stimulation Of

We describe here the stimulation by pancreastatin of 1,2-diacylglycerol production and protein kinase C activity in liver plasma membrane and isolated hepatocytes. The dose-dependency for the stimulation of both processes was similar to the recently described pattern of glucose output and cytosolic Ca2+ transients produced by pancreastatin. The time course of diacylglycerol production at 30 degrees C showed a rapid increase within 5 min, reaching a maximum at 10 min. Protein kinase C from hepatocytes was dependent on Ca2+ and phosphatidylserine. Neither the pancreastatin-stimulated diacylglycerol production nor the activation of protein kinase C was affected by pretreatment with pertussis toxin. However, the presence of GTP partially inhibited this pancreastatin stimulation of 1,2-diacylglycerol in a dose-dependent manner, although GTP alone stimulates diacylglycerol accumulation. This inhibitory effect of GTP on pancreastatin stimulation of diacylglycerol synthesis was completely abolished by the pretreatment with pertussis toxin. In conclusion, this study provides evidence that pancreastatin stimulates the formation of 1,2-diacylglycerol by a pertussis-toxin-independent mechanism, which may be responsible for the pancreastatin activation of protein kinase C.

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