scholarly journals Role of fructose 2,6-bisphosphate in the control by glucagon of gluconeogenesis from various precursors in isolated rat hepatocytes

1984 ◽  
Vol 218 (1) ◽  
pp. 165-170 ◽  
Author(s):  
L Hue ◽  
R Bartrons
Keyword(s):  
Pyruvate Kinase ◽  
Glucose Production ◽  
Rat Hepatocytes ◽  
Isolated Rat Hepatocytes ◽  
Lactate And Pyruvate ◽  
Isolated Rat

Hepatocytes from overnight-starved rats were incubated with 1-20 mM-fructose, -dihydroxyacetone, -glycerol, -alanine or -lactate and -pyruvate with or without 0.1 microM-glucagon. The production of glucose and lactate was measured, as was the content of fructose 2,6-bisphosphate. The concentrations of fructose (below 5 mM) and dihydroxyacetone (above 1 mM) that gave rise to an increase in fructose 2,6-bisphosphate were those at which a glucagon effect on the production of glucose and lactate could be observed. Glycerol had no effect on fructose 2,6-bisphosphate content or on production of lactate, and glucagon did not stimulate the production of glucose from this precursor. With alanine or lactate/pyruvate as substrates, glucagon stimulated glucose production whether the concentration of fructose 2,6-bisphosphate was increased or not. The extent of inactivation of pyruvate kinase by glucagon was not affected by the presence of the various gluconeogenic precursors. The role of fructose 2,6-bisphosphate in the effect of glucagon on gluconeogenesis from precursors entering the pathway at the level of triose phosphates or pyruvate is discussed.

Effects of chronic uraemia on the formation of glucose and urea plus ammonia from l-alanine, l-glutamine and l-serine in isolated rat hepatocytes

1986 ◽  
Vol 70 (6) ◽  
pp. 627-634 ◽  
Author(s):  
Rita A. Klim ◽  
Marta Albajar ◽  
Reginald Hems ◽  
Dermot H. Williamson
Keyword(s):  
Glucose Production ◽  
Rat Hepatocytes ◽  
Nitrogen Release ◽  
Isolated Rat Hepatocytes ◽  
Metabolic Intermediates ◽  
Chronic Uraemia ◽  
Serine Dehydratase ◽  
Glucose Synthesis ◽  
Lactate And Pyruvate ◽  
Isolated Rat

1. The effects of chronic uraemia on glucose production and nitrogen release (urea plus ammonia formation) from alanine, glutamine or serine in isolated rat hepatocytes were studied. 2. Uraemia increased the rate of formation of urea plus ammonia from all three amino acids by 38-93% when they were present at a final concentration of 10 mmol/l. At lower concentrations (2 mmol/l) the rate of nitrogen release was not significantly increased. 3. Hepatocytes from normal rats whose food intake had been restricted to the level of that of uraemic rats did not show the increased rates of nitrogen release. 4. The increased rates of nitrogen release with hepatocytes from uraemic rats were not accompanied by increased rates of glucose synthesis. Instead, accumulation of metabolic intermediates occurred: lactate and pyruvate (alanine or serine as substrates) and glutamate (glutamine as substrate). 5. Livers of uraemic rats had increased activities of glutarninase (30%) and serine dehydratase (100%). 6. Hepatocytes from normal rats treated with phlorhizin to increase the plasma glucagon/insulin ratio behaved in a similar manner to hepatocytes from uraemic rats. They had increased serine dehydratase activity, and increased rates of utilization of serine or glutamine. 7. The possible implications of these findings for human uraemia are discussed.

scholarly journals The rôle of mitochondrial pyruvate transport in the stimulation by glucagon and phenylephrine of gluconeogenesis from l-lactate in isolated rat hepatocytes

1981 ◽  
Vol 198 (3) ◽  
pp. 551-560 ◽  
Author(s):  
A P Thomas ◽  
A P Halestrap
Keyword(s):  
Pyruvate Kinase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Production ◽  
Rat Hepatocytes ◽  
Pyruvate Kinase Activity ◽  
Isolated Rat Hepatocytes ◽  
Isolated Liver Cells ◽  
Additional Role ◽  
Isolated Liver

The sensitivity of glucose production from L-lactate by isolated liver cells from starved rats to inhibition by alpha-cyano-4-hydroxycinnamate was studied. A small percentage of the maximal rate of gluconeogenesis was insensitive to inhibition by alpha-cyano-4-hydroxycinnamate, and evidence is presented to show that this is due to pyruvate entry into the mitochondria as alanine. After subtraction of this rate, Dixon plots of the reciprocal of the rate of gluconeogenesis against inhibitor concentration were linear both in the absence and presence of glucagon, phenylephrine or valinomycin, each of which stimulated gluconeogenesis by 30-50%. Pyruvate kinase activity was decreased by glucagon, but not by phenylephrine or valinomycin. Inhibition of gluconeogenesis by quinolinate (inhibitor of phosphoenolpyruvate carboxykinase) or monochloroacetate (probably inhibiting pyruvate carboxylation) caused a significant deviation from linearity of the Dixon plot obtained with alpha-cyano-4-hydroxycinnamate. Amytal, however, inhibited gluconeogenesis without affecting the linearity of this plot. These data, coupled with a computer simulation study, suggest that pyruvate transport may control gluconeogenesis from L-lactate and that hormones may stimulate this process through an effect on the respiratory chain. An additional role for pyruvate kinase and pyruvate carboxylase is quite compatible with the data presented.

scholarly journals NADP-specific isocitrate dehydrogenase in regulation of urea synthesis in rat hepatocytes

1980 ◽  
Vol 190 (3) ◽  
pp. 581-592 ◽  
Author(s):  
L G Petcu ◽  
G W E Plaut
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Reductive Amination ◽  
Rat Hepatocytes ◽  
Urea Synthesis ◽  
Isolated Rat Hepatocytes ◽  
Lactate And Pyruvate ◽  
Rate Limiting ◽  
Isolated Rat ◽  
Reducing Equivalents

The effect of inhibition of NADP-specific isocitrate dehydrogenase (EC 1.1.1.42) by DL-threo-alpha-methylisocitrate (3-hydroxy-1,2,3-butanetricarboxylase) on urea synthesis was studied in isolated rat hepatocytes. alpha-Methylisocitrate substantially inhibited the rate of urea synthesis (35—84%) with substrates requiring net reductive amination of 2-oxoglutarate to glutamate for aspartate synthesis (i.e., L-serine, D-alanine, or NH4Cl + L-lactate). alpha-Methylisocitrate did not inhibit synthesis of urea from substrates not requiring reductive formation of glutamate (i.e. L-alanine, L-glutamine, L-asparagine, or NH4Cl + L-ornithine). The rate-limiting role of NADPH in urea synthesis was correlated with the decrease in NADPH content that occurred upon addition of NH4Cl or of alpha-methylisocitrate to hepatocytes incubated with lactate and pyruvate, indicating utilization of NADPH for reductive amination of 2-oxoglutarate and inhibition of NADPH generation via NADP-isocitrate dehydrogenase, respectively. Similar results were obtained with D-alanine and L-serine; however, alpha-methylisocitrate or NH4Cl did not substantially decrease NADPH content when L-alanine was the substrate. Inhibitors or ornithine—2-oxo acid transaminase (L-canaline or gabaculine) decreased the uptake of ornithine by hepatocytes and inhibited the alpha-methylisocitrate insensitive urea synthesis from ornithine and NH4Cl. Canaline did not inhibit urea synthesis from lactate, ornithine, and NH4Cl but the inhibition by alpha-methylisocitrate of urea formation from this combination was appreciably larger with canaline (approx. 82%) than without canaline (approx. 48%). Inhibition of urea synthesis from NH4Cl + lactate by alpha-methylisocitrate was partially prevented by oleate, octanoate, or 3-hydroxybutyrate. When the NADH content of hepatocytes was increased by 3-hydroxybutyrate, the addition of NH4Cl and/or alpha-methylisocitrate caused a decline in NADH (and NADPH) content, suggesting that reducing equivalents from NADH as well as from NADPH can support net reductive amination of 2-oxoglutarate when required for urea synthesis.

P413 ROLE OF KINASES EGFR AND SRC IN ESTRADIOL 17β-GLUCURONIDE (E17G) INDUCED CHOLESTASIS IN ISOLATED RAT HEPATOCYTES COUPLETS (IRHC)

2014 ◽  
Vol 60 (1) ◽  
pp. S205-S206
Author(s):  
I.R. Barosso ◽  
A.E. Zucchetti ◽  
G.S. Miszczuk ◽  
M.G. Roma ◽  
F.A. Crocenzi ◽  
...  
Keyword(s):  
Rat Hepatocytes ◽  
Isolated Rat Hepatocytes ◽  
Estradiol 17Β ◽  
Isolated Rat

scholarly journals Calcium rather than cyclic AMP is an intracellular messenger of parathyroid hormone action on glycogen metabolism in isolated rat hepatocytes

1989 ◽  
Vol 258 (3) ◽  
pp. 889-894 ◽  
Author(s):  
T Mine ◽  
I Kojima ◽  
E Ogata
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Glucose Production ◽  
Rat Hepatocytes ◽  
Free Calcium ◽  
Dependent Manner ◽  
Isolated Rat Hepatocytes ◽  
Glucose Output ◽  
Dose Dependent ◽  
Isolated Rat

The synthetic 1-34 fragment of human parathyroid hormone (1-34hPTH) stimulated glucose production in isolated rat hepatocytes. The effect of 1-34hPTH was dose-dependent and 10(10) M-1-34 hPTH elicited the maximum glucose output, which was approx. 80% of that by glucagon. Although 1-34hPTH induced a small increase in cyclic AMP production at concentrations higher than 10(-9) M, 10(-10) M-1-34hPTH induced the maximum glucose output without significant elevation of cyclic AMP. This is in contrast to the action of forskolin, which increased glucose output to the same extent as 10(-10) M-1-34hPTH by causing a 2-fold elevation of cyclic AMP. In addition to increasing cyclic AMP, 1-34hPTH caused an increase in cytoplasmic free calcium concentration ([Ca2+]c). When the effect of 1-34hPTH on [Ca2+]c was studied in aequorin-loaded cells, low concentrations of 1-34hPTH increased [Ca2+]c: the 1-34hPTH effect on [Ca2+]c was detected at as low as 10(-12) M and increased in a dose-dependent manner. 1-34hPTH increased [Ca2+]c even in the presence of 1 microM extracellular calcium, suggesting that PTH mobilizes calcium from an intracellular pool. In line with these observations, 1-34hPTH increased the production of inositol trisphosphate. These results suggest that: (1) PTH activates both cyclic AMP and calcium messenger systems and (2) PTH stimulates glycogenolysis mainly via the calcium messenger system.

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