scholarly journals Difference in glucose sensitivity of liver glycolysis and glycogen synthesis. Relationship between lactate production and fructose 2,6-bisphosphate concentration

1984 ◽  
Vol 224 (3) ◽  
pp. 779-786 ◽  
Author(s):  
L Hue ◽  
F Sobrino ◽  
L Bosca
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Rat Hepatocytes ◽  
Isolated Rat Hepatocytes ◽  
Cytosolic Proteins ◽  
Glucose Injection ◽  
Opposite Situation ◽  
Glucose Sensitivity ◽  
Fructose 1,6 Bisphosphate

Incubation of isolated rat hepatocytes from fasted rats with 0-6 mM-glucose caused an increase in [fructose 2,6-bisphosphate] (0.2 to about 5 nmol/g) without net lactate production. A release of 3H2O from [3-3H]glucose was, however, detectable, indicating that phosphofructokinase was active and that cycling occurred between fructose 6-phosphate and fructose 1,6-bisphosphate. A relationship between [fructose 2,6-bisphosphate] and lactate production was observed when hepatocytes were incubated with [glucose] greater than 6 mM. Incubation with glucose caused a dose-dependent increase in [hexose 6-phosphates]. The maximal capacity of liver cytosolic proteins to bind fructose 2,6-bisphosphate was 15 nmol/g, with affinity constants of 5 × 10(6) and 0.5 × 10(6) M-1. One can calculate that, at 5 microM, more than 90% of fructose 2,6-bisphosphate is bound to cytosolic proteins. In livers of non-anaesthetized fasted mice, the activation of glycogen synthase was more sensitive to glucose injection than was the increase in [fructose 2,6-bisphosphate], whereas the opposite situation was observed in livers of fed mice. Glucose injection caused no change in the activity of liver phosphofructokinase-2 and decreased the [hexose 6-phosphates] in livers of fed mice.

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.

Fatty acid and amino acid modulation of glucose cycling in isolated rat hepatocytes

2001 ◽  
Vol 358 (3) ◽  
pp. 665-671 ◽  
Author(s):  
Lori A. GUSTAFSON ◽  
Mies NEEFT ◽  
Dirk-Jan REIJNGOUD ◽  
Folkert KUIPERS ◽  
Hans P. SAUERWEIN ◽  
...  
Keyword(s):  
Amino Acids ◽  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Lactate Production ◽  
Rat Hepatocytes ◽  
Glycolytic Flux ◽  
Isolated Rat Hepatocytes ◽  
Glycogen Accumulation ◽  
Glycogen Deposition ◽  
Intracellular Glucose

We studied the influence of glucose/glucose 6-phosphate cycling on glycogen deposition from glucose in fasted-rat hepatocytes using S4048 and CP320626, specific inhibitors of glucose-6-phosphate translocase and glycogen phosphorylase respectively. The effect of amino acids and oleate was also examined. The following observations were made: (1) with glucose alone, net glycogen production was low. Inhibition of glucose-6-phosphate translocase increased intracellular glucose 6-phosphate (3-fold), glycogen accumulation (5-fold) without change in active (dephosphorylated) glycogen synthase (GSa) activity, and lactate production (4-fold). With both glucose 6-phosphate translocase and glycogen phosphorylase inhibited, glycogen deposition increased 8-fold and approached reported in vivo rates of glycogen deposition during the fasted → fed transition. Addition of a physiological mixture of amino acids in the presence of glucose increased glycogen accumulation (4-fold) through activation of GS and inhibition of glucose-6-phosphatase flux. Addition of oleate with glucose present decreased glycolytic flux and increased the flux through glucose 6-phosphatase with no change in glycogen deposition. With glucose 6-phosphate translocase inhibited by S4048, oleate increased intracellular glucose 6-phosphate (3-fold) and net glycogen production (1.5-fold), without a major change in GSa activity. It is concluded that glucose cycling in hepatocytes prevents the net accumulation of glycogen from glucose. Amino acids activate GS and inhibit flux through glucose-6-phosphatase, while oleate inhibits glycolysis and stimulates glucose-6-phosphatase flux. Variation in glucose 6-phosphate does not always result in activity changes of GSa. Activation of glucose 6-phosphatase flux by fatty acids may contribute to the increased hepatic glucose production as seen in Type 2 diabetes.

scholarly journals Nitric oxide inhibits glycogen synthesis in isolated rat hepatocytes

1998 ◽  
Vol 330 (2) ◽  
pp. 1045-1049 ◽  
Author(s):  
Fleur SPRANGERS ◽  
P. Hans SAUERWEIN ◽  
A. Johannes ROMIJN ◽  
M. George van WOERKOM ◽  
J. Alfred MEIJER
Keyword(s):  
Nitric Oxide ◽  
Glucose Metabolism ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Rat Hepatocytes ◽  
Inhibitory Effect ◽  
No Donor ◽  
Isolated Rat Hepatocytes ◽  
Intracellular Glucose

There is increasing evidence for the existence of intrahepatic regulation of glucose metabolism by Kupffer cell products. Nitric oxide (NO) is known to inhibit gluconeogenic flux through pyruvate carboxylase and phosphoenolpyruvate carboxykinase. However, NO may also influence glucose metabolism at other levels. Using hepatocytes from fasted rats incubated with the NO-donor S-nitroso-N-acetylpenicillamine, we have now found that the synthesis of glycogen from glucose is even more sensitive to inhibition by NO than gluconeogenesis. Inhibition of glycogen production by NO was accompanied by a rise in intracellular glucose 6-phosphate and UDPglucose. Activity of glycogen synthase, as measured in extracts of hepatocytes after the cells had been exposed to NO, was decreased. Experiments with gel-filtered liver extracts revealed that inhibition of glycogen synthase was caused by an inhibitory effect of NO on the conversion of glycogen synthase b into glycogen synthase a.

scholarly journals Epidermal growth factor mimics insulin effects in rat hepatocytes

1986 ◽  
Vol 239 (3) ◽  
pp. 523-530 ◽  
Author(s):  
F Bosch ◽  
B Bouscarel ◽  
J Slaton ◽  
P F Blackmore ◽  
J H Exton
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cyclic Amp ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Rat Hepatocytes ◽  
Maximum Effect ◽  
Similar Time ◽  
Isolated Rat Hepatocytes ◽  
Epidermal Growth

Epidermal growth factor (EGF) mimicked the effect of insulin to activate glycogen synthase and stimulate glycogen synthesis in isolated rat hepatocytes. Both agents required glucose (greater than 5 mM) and had similar time courses of action. The maximum effect of EGF was approx. 70% of that of insulin, and the half-maximally effective concentrations were 9 nM and 4 nM respectively. Combinations of the two agents produced additive responses. EGF also resembled insulin in its ability to inhibit the effects of 0.1-1.0 nM-glucagon on cyclic AMP and glycogen phosphorylase in hepatocytes. The maximum effect of EGF was approx. 70% of that of insulin, and the half-maximally effective concentrations were approx. 5 nM and 0.5 nM respectively. EGF and insulin inhibited phosphorylase activation by exogenous cyclic AMP, and inhibited cyclic AMP accumulation induced by forskolin. They also inhibited phosphorylase activation provoked by phenylephrine, but not by vasopressin. EGF added alone rapidly activated phosphorylase and increased cytosolic [Ca2+], but the effects were no longer apparent at 5 min and were smaller than those of vasopressin. Insulin did not induce these changes. In hepatocytes previously incubated with myo-[3H]inositol, EGF did not significantly increase myo-inositol 1,4,5-trisphosphate. However, its ability to increase cytosolic [Ca2+] was blocked by neomycin, an inhibitor of phosphatidylinositol bisphosphate hydrolysis. It is concluded that some, but not all, of the effects of EGF in liver are strikingly similar to those exerted by insulin, suggesting that these agents may have some similar mechanisms of action in this tissue.

scholarly journals Control of glycogen synthase phosphorylation in isolated rat hepatocytes by epinephrine, vasopressin and glucagon

1984 ◽  
Vol 142 (3) ◽  
pp. 511-520 ◽  
Author(s):  
Carlos CIUDAD ◽  
Marcella CAMICI ◽  
Zafeer AHMAD ◽  
Yuhuan WANG ◽  
Anna A. DePAOLI-ROACH ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Rat Hepatocytes ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat

scholarly journals Pancreastatin is an endogenous peptide that regulates glucose homeostasis

2013 ◽  
Vol 45 (22) ◽  
pp. 1060-1071 ◽  
Author(s):  
Guru Raghavendra Valicherla ◽  
Zakir Hossain ◽  
Sushil K. Mahata ◽  
Jiaur R. Gayen
Keyword(s):  
Glucose Homeostasis ◽  
Uncoupling Protein ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Rat Hepatocytes ◽  
Negative Regulator ◽  
Metabolic Effects ◽  
Free Calcium ◽  
Porcine Pancreas ◽  
Signaling Mechanism

Pancreastatin (PST) is a regulatory peptide containing 49 amino acids, first isolated from porcine pancreas. Intracellular and extracellular processing of the prohormone Chromogranin A (Chga) results various bioactive peptides of which PST has dysglycemic activity. PST regulates glucose, lipid, and protein metabolism in liver and adipose tissues. It also regulates the secretion of leptin and expression of leptin and uncoupling protein 2 in adipose tissue. In Chga knockout mice, PST induces gluconeogenesis in the liver. PST reduces glucose uptake in mice hepatocytes and adipocytes. In rat hepatocytes, PST induces glycogenolysis and glycolysis and inhibits glycogen synthesis. In rat adipocytes, PST inhibits lactate production and lipogenesis. These metabolic effects are confirmed in humans. In the dual signaling mechanism of PST receptor, mostly PST activates Gαq/11 protein leads to the activation of phospholipase C β3-isoform, therefore increasing cytoplasmic free calcium and stimulating protein kinase C. PST inhibits the cell growth in rat HTC hepatoma cells, mediated by nitric oxide and cyclic GMP production. Elevated levels of PST correlating with catecholamines have been found in gestational diabetes and essential hypertension. Rise in the blood PST level in Type 2 diabetes suggests that PST is a negative regulator of insulin sensitivity and glucose homeostasis.

scholarly journals The effects of recombinant tumour necrosis factor (cachectin) on metabolism in isolated rat adipocyte, hepatocyte and muscle preparations

1987 ◽  
Vol 247 (3) ◽  
pp. 789-792 ◽  
Author(s):  
A M Rofe ◽  
R A J Conyers ◽  
R Bais ◽  
J R Gamble ◽  
M A Vadas
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Lactate Production ◽  
Rat Hepatocytes ◽  
Short Term ◽  
Isolated Rat Hepatocytes ◽  
Fatty Acid Release ◽  
14Co2 Production ◽  
Necrosis Factor ◽  
Isolated Rat

Tumour necrosis factor (TNF) did not stimulate lipolysis in isolated rat adipocytes, though preincubation with TNF increased adrenaline-stimulated fatty acid release. Glycogenolysis, gluconeogenesis and ketogenesis in isolated rat hepatocytes were not influenced by TNF in short-term (30-60 min) incubations. TNF stimulated 14CO2 production from [U-14C]glucose in rat hemidiaphragm preparations, but lactate production and alanine release were not significantly altered. It is concluded that TNF does not regulate short-term metabolism in adipocytes, hepatocytes and muscle preparations in the manner of a catabolic hormone.

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