Inhibition of Urea and Glucose Production by Acetazolahide in Isolated Rat Hepatocytes

1984 ◽  
Vol 67 (s9) ◽  
pp. 15P-16P
Author(s):  
J.P. Monson ◽  
H.K. Metcalfe ◽  
P.J. Drew ◽  
R.A. Iles ◽  
N.D. Carter ◽  
...  
Keyword(s):  
Glucose Production ◽  
Rat Hepatocytes ◽  
Isolated Rat Hepatocytes ◽  
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.

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 Differential effects of tryptophan on glucose synthesis in rats and guinea pigs

1978 ◽  
Vol 176 (3) ◽  
pp. 817-825 ◽  
Author(s):  
S A Smith ◽  
K R F Elliott ◽  
C I Pogson
Keyword(s):  
Rat Liver ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Production ◽  
Rat Hepatocytes ◽  
Liver Cells ◽  
Isolated Rat Hepatocytes ◽  
Rat Liver Cells ◽  
Glucose Output ◽  
Isolated Rat

1. Tryptophan inhibition of gluconeogenesis in isolated rat liver cells is characterized by a 20 min lag period before linear rates of glucose output are attained. 2. Half-maximal inhibition of gluconeogenesis in isolated rat hepatocytes is produced by approx. 0.1 mM-tryptophan. 3. Tryptophan inhibits gluconeogenesis from all substrates giving rise to oxaloacetate, but stimulates glycerol-fuelled glucose production. 4. Gluconeogenesis in guinea-pig hepatocytes is insensitive to tryptophan. 5. Changes in metabolite concentrations in rat liver cells are consistent with a locus of inhibition at the step catalysed by phosphoenolpyruvate carboxykinase. 6. Inhibition of gluconeogenesis persists in cells from rats pretreated with tryptophan in vivo. 7. Tryptophan has no effect on urea production from alanine, but decreases [1-14C]palmitate oxidation to 14CO2 and is associated with an increased [hydroxybutyrate]/[acetoacetate] ratio. 8. These results are discussed with reference to the control of gluconeogenesis in various species.

Stimulation of Glucose Production by Activin-A in Isolated Rat Hepatocytes*

Endocrinology ◽  
1989 ◽  
Vol 125 (2) ◽  
pp. 586-591 ◽  
Author(s):  
TETSUYA MINE ◽  
ITARU KOJIMA ◽  
ETSURO OGATA
Keyword(s):  
Glucose Production ◽  
Rat Hepatocytes ◽  
Activin A ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat ◽  
Stimulation Of

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.

Iron deficiency decreases gluconeogenesis in isolated rat hepatocytes

1989 ◽  
Vol 67 (5) ◽  
pp. 1868-1872 ◽  
Author(s):  
K. L. Klempa ◽  
W. T. Willis ◽  
R. Chengson ◽  
P. R. Dallman ◽  
G. A. Brooks
Keyword(s):  
Iron Deficiency ◽  
Glucose Production ◽  
Rat Hepatocytes ◽  
Female Rats ◽  
Glucose Turnover ◽  
Dietary Iron ◽  
Isolated Rat Hepatocytes ◽  
Iron Deficient ◽  
Isolated Rat

Dietary iron deficiency in rats results in increased blood glucose turnover and recycling. We measured the rates of glucose production in isolated hepatocytes from iron-sufficient (Fe+) and iron-deficient (Fe-) rats to assess the intrinsic capacity of the Fe- liver to carry out gluconeogenesis. Low-iron and control diets were given to 21-day-old female rats. After 4-5 wk, hemoglobin concentrations averaged 4.1 g/dl in the Fe- and 14.3 g/dl in the Fe+ animals. In the hepatocytes from Fe- rats, there was a 35% decrease in the rate of glucose production from 1 mM pyruvate + 10 mM lactate, a 48% decrease from 0.1 mM pyruvate + 1 mM lactate, a 39% decrease from 1 mM alanine, and a 48% decrease from 1 mM glycerol. The addition of 5 microM norepinephrine or 0.5 microM glucagon to the incubation media produced stimulatory effects on hepatocytes from both Fe- and Fe+ rats, resulting in the maintenance of an average difference of 38% in the rates of gluconeogenesis between the two groups. Studies on isolated liver mitochondria and cytosol revealed alpha-glycerophosphate-cytochrome c reductase and phospho(enol)pyruvate carboxykinase activities to be decreased by 27% in Fe- rats. We conclude that because severe dietary iron deficiency decreases gluconeogenesis in isolated rat hepatocytes, the increased gluconeogenesis demonstrated by Fe- rats in vivo is attributable to increased availability of gluconeogenic substrates and upregulation of the pathway.

scholarly journals Pancreastatin increases free cytosolic Ca2+ in rat hepatocytes, involving both pertussis-toxin-sensitive and -insensitive mechanisms

1993 ◽  
Vol 294 (2) ◽  
pp. 439-442 ◽  
Author(s):  
V Sánchez-Margalet ◽  
M Lucas ◽  
R Goberna
Keyword(s):  
Pertussis Toxin ◽  
Glucose Production ◽  
Rat Hepatocytes ◽  
Regulatory Proteins ◽  
Sudden Increase ◽  
Specific Receptor ◽  
Isolated Rat Hepatocytes ◽  
Vasopressin Antagonist ◽  
Adrenergic Blocker ◽  
Isolated Rat

Freshly isolated rat hepatocytes, loaded with the Ca2+ probe Fluo-3, responded to homologous pancreastatin with a sudden increase in free cytosolic Ca2+ ([Ca2+]i) as well as glucose release. Addition of rat pancreastatin (0.1 microM) to hepatocytes resulted in an increase in [Ca2+]i from 150 nM to 700 nM, which declined back to nearly basal values within 2-3 min. Half-maximal and maximal effects were observed at 0.3 and 100 nM pancreastatin respectively. The increase in [Ca2+]i induced by vasopressin and noradrenaline was very similar in extent (from 150 to 800 nM) to that produced by pancreastatin. Neither the alpha 1-adrenergic blocker prazosin nor the vasopressin antagonist V1 modified the increase in [Ca2+]i induced by pancreastatin. Pig pancreastatin and its 33-49 C-terminal fragment produced about 65 and 75% of the effect of homologous pancreastatin respectively. Glucose production correlated with changes in [Ca2+]i in the same order of potency: vasopressin > rat pancreastatin > pig 33-49 pancreastatin > pig 1-49 pancreastatin. The effect of pancreastatin on [Ca2+]i was decreased by 50% when Ca2+ was omitted from the medium, and totally abolished when hepatocytes were depleted of internal Ca2+ stores by preincubation without Ca2+ and with 2 mM EGTA. When hepatocytes were preincubated for 5 min with PMA, the effects of ATP and noradrenaline were prevented, and those of vasopressin and pancreastatin remained unchanged. The pretreatment of hepatocytes with pertussis toxin diminished the response to pancreastatin and vasopressin. These results suggest that pancreastatin is a new Ca(2+)-mobilizing glycogenolytic hormone acting through a specific receptor which may involve both pertussis-toxin-sensitive and -insensitive GTP-binding regulatory proteins.

Sign in / Sign up

Export Citation Format

Share Document