Studies on regulatory mechanisms of heme biosynthesis in hepatocytes from normal and experimental-diabetic rats. Role of cAMP

1989 ◽  
Vol 67 (11-12) ◽  
pp. 751-758 ◽  
Author(s):  
Eduardo T. Cánepa ◽  
Elena B. C. Llambías ◽  
Moisés Grinstein
Keyword(s):  
Aminolevulinic Acid ◽  
Rat Hepatocytes ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Intracellular Camp ◽  
Induction Effect ◽  
Isolated Rat Hepatocytes ◽  
Camp Content ◽  
Cytochrome P 450 ◽  
Phenobarbital Induction

In the present work we have been able to demonstrate the existence of some interrelationship between intracellular level of cAMP content and phenobarbital induction of δ-aminolevulinic acid synthase, ferrochelatase, and cytochrome P-450 biosynthesis in isolated rat hepatocytes. The increase of the level of intracellular cAMP produced by activators of adenylate cyclase, inhibitors of phosphodiesterase, or added cyclic nucleotides is reflected by an increase of the phenobarbital induction effect. The greater induction observed in hepatocytes of diabetic rats may be due to a higher level of the intracellular cAMP. The lack of potentiation of added cAMP in diabetic cells is mainly due to the fact that the maximum induction that could be attained is already achieved by the effect of the preexisting high level of the endogenous cAMP.Key words: δ-aminolevulinic acid synthase, ferrochelatase, cytochrome P-450, cAMP, diabetic rat hepatocytes.

Studies on regulatory mechanisms of heme biosynthesis in hepatocytes from normal and experimental-diabetic rats. Role of insulin

1990 ◽  
Vol 68 (6) ◽  
pp. 914-921 ◽  
Author(s):  
Eduardo T. Cánepa ◽  
Elena B. C. Llambías ◽  
Moisés Grinstein
Keyword(s):  
Aminolevulinic Acid ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Significant Inhibition ◽  
Diabetic Rat ◽  
Experimental Conditions ◽  
Cytochrome P 450

In the present work we demonstrate that insulin decreases the phenobarbital-induced activities of δ-aminolevulinic acid synthase and ferrochelatase in isolated hepatocytes from normal and experimental-diabetic rats. Insulin concentrations required to produce significant inhibition in diabetic hepatocytes were higher than in normal cells. Under similar experimental conditions, insulin decreased the basal activities of δ-aminolevulinic acid synthase and ferrochelatase in hepatocytes from normal rats; no inhibitory effect was observed on the basal activity of δ-aminolevulinic acid synthase in hepatocytes from diabetic rats. Cytochrome P-450 content of both normal and diabetic cells was not affected by insulin in absence or presence of phenobarbital. The inhibitory action of insulin was exerted even when effective concentrations of glucagon, dexamethasone, or 8-(p-chlorophenylthio)-cAMP were present.Key words: δ-aminolevulinic acid synthase, ferrochelatase, cAMP, insulin, diabetic rat hepatocytes.

Effect of experimental diabetes on rat cardiac cAMP, phosphorylase, and inotropy

1983 ◽  
Vol 244 (6) ◽  
pp. H844-H851 ◽  
Author(s):  
R. V. Vadlamudi ◽  
J. H. McNeill
Keyword(s):  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Phosphorylase Activity ◽  
Camp Content ◽  
Rat Hearts ◽  
Underlying Causes ◽  
Camp Levels ◽  
Working Rat Heart ◽  
Time Point

The isolated perfused working rat heart was used to study experimental diabetes-induced alterations in the effect of isoproterenol on adenosine 3',5'-cyclic monophosphate (cAMP) content, inotropy, and phosphorylase activity. Experimental diabetes was induced by intravenous injection of either alloxan (40 mg/kg) or streptozotocin (50 mg/kg). There were no changes in either basal cAMP levels or in isoproterenol-induced cAMP levels in hearts from diabetic rats at either 3 days or 100-120 days after induction of diabetes. Maximum changes produced by isoproterenol in positive and negative dP/dt developments of diabetic rat hearts were also not different from control at either time point. However, phosphorylase was activated to a significantly greater extent by isoproterenol in hearts obtained from acute as well as chronic diabetic rats. Chronic diabetic rat hearts exhibited significantly higher total phosphorylase activity. Diabetic rat hearts had slightly but not significantly higher basal phosphorylase a activity. Furthermore, prostaglandin E1 activated phosphorylase in diabetic rat hearts but not in control rat hearts. Acute metabolic derangements and alterations in Ca2+ homeostasis caused by diabetes could be the underlying causes for this phosphorylase response. Thyroid hormone levels were depressed in diabetic rats. However, hypothyroidism is probably not responsible for the alterations in phosphorylase activity.

scholarly journals EFFECT OF MURRAYA KOENIGII LEAVES EXTRACT ON GLUCONEOGENESIS AND GLYCOGENOLYSIS IN ISOLATED RAT HEPATOCYTES CULTURE

2018 ◽  
Vol 11 (11) ◽  
pp. 264
Author(s):  
Rohan S Phatak ◽  
Chitra C Khanwelkar ◽  
Kailas D Datkhile ◽  
Pratik P Durgawale
Keyword(s):  
Glycogen Content ◽  
Ex Vivo ◽  
Rat Hepatocytes ◽  
Diabetic Rats ◽  
Murraya Koenigii ◽  
Isolated Rat Hepatocytes ◽  
Genes Expression ◽  
Different Doses ◽  
Isolated Rat

Objectives: The present study was aimed to investigate the in vitro activity of Murraya koenigii extracts through various carbohydrate metabolic pathways in the isolated rat hepatocyte models.Methods: Different doses of metformin, aqueous and methanol extracts of M. koenigii leaves were evaluated in the MTT, glucose, and glycogen content assays in the cultured in vitro rat hepatocytes.Results: The study showed that there was a significant increase in activity with respect to the increased concentration of extracts. Slight effect was observed in the isolated rat hepatocytes culture, M. koenigii leaves extract may exert cytoprotective and hypoglycemic action.Conclusion: It may be needed to determine the effect of ex vivo rat hepatocytes isolated from diabetic rats. Effects of the plant or isolated compounds on the genes expression of signaling pathways should be investigated in further studies.

scholarly journals N-alkylation of exogenous haem analogues caused by drugs in isolated hepatocytes. Structural isomerism and chirality of the resulting porphyrins

1986 ◽  
Vol 238 (1) ◽  
pp. 263-268 ◽  
Author(s):  
F De Matteis ◽  
C Harvey ◽  
S R Martin
Keyword(s):  
Direct Evidence ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Isomeric Composition ◽  
Isolated Rat Hepatocytes ◽  
Structural Isomerism ◽  
Cytochrome P 450 ◽  
Isolated Rat ◽  
Suicide Substrates

Isolated rat hepatocytes incubated with two suicide substrates of cytochrome P-450, 2-allyl-2-isopropylacetamide and 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine(4-ethyl-DD C), convert exogenous mesohaem and deuterohaem into N-alkylated mesoporphyrins and deuteroporphyrins respectively. The N-alkylated mesoporphyrins can be separated by h.p.l.c. from the corresponding N-alkylated protoporphyrins originating from endogenous haem; in this way the contribution of both endogenous and exogenous pools of haem can be studied in the same experiment. N-Alkylated mesoporphyrin exhibits chiral properties, and its isomeric composition and/or amount are dependent on the particular cytochrome P-450 enzyme predominating in the cell. These findings provide additional and more direct evidence that exchangeable haem is taken up by cytochrome P-450 before being N-alkylated.

scholarly journals Insulin effects on apolipoprotein B production by normal, diabetic and treated-diabetic rat liver and cultured rat hepatocytes

1989 ◽  
Vol 261 (1) ◽  
pp. 83-88 ◽  
Author(s):  
J D Sparks ◽  
C E Sparks ◽  
L L Miller
Keyword(s):  
Primary Cultures ◽  
Rat Hepatocytes ◽  
Insulin Injection ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Apo B ◽  
Hormone Effect ◽  
Daily Insulin Injection ◽  
The Media ◽  
Rat Livers

1. The effect of insulin on apolipoprotein (apo B) secretion was studied in 24 h recirculating liver perfusions of isolated normal, diabetic and insulin-treated diabetic rats. In single perfusions from each group apo B accumulated in the media in a linear fashion. 2 In perfusions of normal rat livers, when the medium contained insulin plus cortisol, apo B production was significantly inhibited (by 35.8%), demonstrating a hormone effect on apo B secretion. 3. In perfusions of diabetic-rat livers, apo B production was decreased to 11.8% of normal when the medium contained no hormones, and was not significantly changed by the addition of insulin plus cortisol to the medium, suggesting that the hormone effect on apo B secretion is missing in long-term hypoinsulinaemic states. 4. Treatment of diabetic rats with daily insulin injection restored apo B production and restored the effect of insulin plus cortisol in the medium to inhibit apo B secretion during perfusion. 5. Parallel studies of apo B secretion with insulin alone, cortisol alone and insulin plus cortisol in the medium were performed in primary cultures of hepatocytes to compare results from liver perfusions. 6. Apo B secretion by hepatocytes from normal, diabetic and treated-diabetic rats was inhibited (by 36.8%, 57.1% and 57.9% respectively) when insulin alone was added to the medium. 7. Insulin plus cortisol inhibited apo B secretion by hepatocytes from normal and treated diabetic rats (by 30.2% and 47.2% respectively), but failed to inhibit apo B secretion by hepatocytes from diabetic rats.

scholarly journals Stimulation of glycogen synthesis and lipogenesis by glutamine in isolated rat hepatocytes

1987 ◽  
Vol 248 (2) ◽  
pp. 429-437 ◽  
Author(s):  
A Lavoinne ◽  
A Baquet ◽  
L Hue
Keyword(s):  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Rat Hepatocytes ◽  
Diabetic Rats ◽  
Purine Analogues ◽  
Isolated Rat Hepatocytes ◽  
Body Production ◽  
Stimulation Of

Glutamine stimulated glycogen synthesis and lactate production in hepatocytes from overnight-fasted normal and diabetic rats. The effect, which was half-maximal with about 3 mM-glutamine, depended on glucose concentration and was maximal below 10 mM-glucose. beta-2-Aminobicyclo[2.2.1.]heptane-2-carboxylic acid, an analogue of leucine, stimulated glutaminase flux, but inhibited the stimulation of glycogen synthesis by glutamine. Various purine analogues and inhibitors of purine synthesis were found to inhibit glycogen synthesis from glucose, but they did not abolish the stimulatory effect of glutamine on glycogen synthesis. The correlation between the rate of glycogen synthesis and synthase activity suggested that the stimulation of glycogen synthesis by glutamine depended solely on the activation of glycogen synthase. This activation of synthase was not due to a change in total synthase, nor was it caused by a faster inactivation of glycogen phosphorylase, as was the case after glucose. It could, however, result from a stimulation of synthase phosphatase, since, after the addition of 1 nM-glucagon or 10 nM-vasopressin, glutamine did not interfere with the inactivation of synthase, but did promote its subsequent re-activation. Glutamine was also found to inhibit ketone-body production and to stimulate lipogenesis.

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