scholarly journals Involvement of glucokinase translocation in the mechanism by which resorcinol inhibits glycolysis in hepatocytes

1997 ◽  
Vol 325 (3) ◽  
pp. 667-673 ◽  
Author(s):  
Loranne AGIUS
Keyword(s):  
Glucose Concentration ◽  
Glycogen Synthesis ◽  
High Glucose Concentration ◽  
Phosphate Content ◽  
Maximal Inhibition ◽  
Independent Mechanism ◽  
Elevated Glucose ◽  
Inhibition Of Glycolysis ◽  
Low Activity ◽  
Stimulation Of

Proglycosyn and resorcinol stimulate glycogen synthesis and inhibit glycolysis in hepatocytes. The former effect is attributed to inactivation of phosphorylase mediated by glucuronidated metabolites. This study investigated the mechanism by which resorcinol inhibits glycolysis. Resorcinol (150 μM) inhibited glycolysis in hepatocytes incubated with glucose (15–35 mM) but not with dihydroxyacetone (10 mM). The inhibition of glycolysis at elevated glucose concentration was associated with inhibition of glucose-induced dissociation of glucokinase and aldolase. The resorcinol concentration that caused half-maximal inhibition (20–43 μM) increased with increasing glucose concentration (15–35 mM). Resorcinol inhibited the translocation of glucokinase and the stimulation of detritiation of [2-3H]glucose and [3-3H]glucose caused by sorbitol (10–200 μM), but it potentiated the stimulation of glycogen synthesis. The inhibition of glycolysis by resorcinol could not be accounted for by diversion of substrate to glycogen. The glucose 6-phosphate content correlated with the free glucokinase activity. Resorcinol counteracted the increase in glucose 6-phosphate and fructose 2,6-bisphosphate caused by elevated glucose concentration or by sorbitol. The suppression of glucose 6-phosphate at high glucose concentration (15–35 mM) could be explained by the low activity of free glucokinase. However, the suppression at 5 mM glucose was due in part to an independent mechanism. The effect of resorcinol on glucokinase translocation was partly counteracted by galactosamine, which suppresses UDP-glucose and inhibits glucuronide formation, and was mimicked by phenol and p-nitrophenol but not by p-nitrophenylglucuronide. It is concluded that resorcinol inhibits glycolysis at elevated glucose concentration or when stimulated by sorbitol through increased glucokinase binding. The results indicate a link between glucuronidation and glucokinase translocation.

Insulin sensitivity of rates of glycolysis and glycogen synthesis in soleus, stripped soleus, epitrochlearis, and hemi-diaphragm muscles isolated from sedentary rats

1983 ◽  
Vol 3 (7) ◽  
pp. 675-679 ◽  
Author(s):  
R. A. J. Challiss ◽  
J. Espinal ◽  
E. A. Newsholme
Keyword(s):  
Fatty Acid ◽  
Glucose Utilization ◽  
Glycogen Synthesis ◽  
Maximal Inhibition ◽  
Maximal Stimulation ◽  
Glucose Fatty Acid Cycle ◽  
Isolated Adipocytes ◽  
Stimulation Of

The effect of insulin concentrations on the rates of glycolysis and glycogen synthesis in four different in vitro rat muscle preparations (intact soleus, stripped soleus, epitrochlearis, and hemi-diaphragm) were investigated: the concentrations of insulin that produced half-maximal stimulation of the rates of these two processes in the four muscle preparations were similar – about 100 μunits/ml. This is at least 10-fold greater than the concentration that produced half-maximal inhibition of lipolysis in isolated adipocytes. Since 100 μunits/ml insulin is outside the normal physiological range in the rat, it is suggested that, in vivo, insulin influences glucose utilization in muscle mainly indirectly, via changes in the plasma fatty acid levels and the ‘glucose/fatty acid cycle’. Consequently the view that insulin stimulates glucose utilization in muscle mainly by a direct effect on membrane transport must be treated with caution.

scholarly journals The contribution of pyruvate cycling to loss of [6-3H]glucose during conversion of glucose to glycogen in hepatocytes: effects of insulin, glucose and acinar origin of hepatocytes

1993 ◽  
Vol 289 (1) ◽  
pp. 255-262 ◽  
Author(s):  
L Agius ◽  
D Tosh ◽  
M Peak
Keyword(s):  
Guinea Pig ◽  
High Glucose ◽  
Glucose Concentration ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glycogen Synthesis ◽  
Rat Hepatocytes ◽  
Human Hepatocytes ◽  
Pyruvate Cycling ◽  
Stimulation Of ◽  
In Cells

1. During conversion of [6-3H,U-14C]glucose to glycogen in liver, loss of 6-3H can occur either by cycling via pyruvate (between glycolysis and gluconeogenesis) or by other mechanisms. We used mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, to determine the extent to which pyruvate cycling contributes to loss of 6-3H during glucose conversion to glycogen in hepatocytes. 2. Mercaptopicolinate increased the 3H/14C ratio in glycogen during incubation of rat, guinea pig, pig and human hepatocytes with [6-3H,U-14C]glucose. The increase in the 3H/14C ratio in glycogen caused by mercaptopicolinate was greater in periportal than in perivenous rat hepatocytes, indicating that cycling of glucose via pyruvate is more prominent in cells with a higher gluconeogenic relative to glycolytic capacity. 3. The effect of mercaptopicolinate on the 3H/14C ratio in glycogen was observed both in the absence and in the presence of insulin, indicating that stimulation of glycogen synthesis by insulin is not associated with inhibition of pyruvate cycling. In rat and guinea pig but not in pig hepatocytes, the effects of mercaptopicolinate on the 3H/14C ratio in glycogen were greater at 10-15 mM glucose than at 30 mM glucose, suggesting diminished cycling via pyruvate at high glucose concentrations. 4. Insulin increased the loss of 6-3H during stimulation of conversion of glucose to glycogen in hepatocytes from all species. This was due in part to an increase in pyruvate cycling and in part to other mechanisms that are not inhibited by mercaptopicolinate. 5. These results suggest that pyruvate cycling is a significant, but not exclusive, component of the loss of 6-3H in the hepatocyte during glucose conversion to glycogen. The extent of pyruvate cycling is dependent on the acinar origin of the hepatocytes and on the glucose concentration and presence of insulin.

scholarly journals Regulation of glycogen synthesis and glycolysis by insulin, pH and cell volume. Interactions between swelling and alkalinization in mediating the effects of insulin

1992 ◽  
Vol 282 (3) ◽  
pp. 797-805 ◽  
Author(s):  
M Peak ◽  
M al-Habori ◽  
L Agius
Keyword(s):  
Cell Volume ◽  
Glycogen Synthesis ◽  
Potassium Acetate ◽  
Cell Swelling ◽  
Osmotic Swelling ◽  
Cation Content ◽  
Alkaline Conditions ◽  
Inhibition Of Glycolysis ◽  
Free Media ◽  
Stimulation Of

The effects of changes in cell volume and pH on glycogen synthesis and glycolysis and their control by insulin were investigated in hepatocyte cultures. 1. Cell acidification, by increasing [CO2] from 2.5% to 5%, inhibited glycolysis and stimulated glycogen synthesis. The inhibition of glycolysis was also observed in Na(+)-free media and when K+ uptake was inhibited, but the stimulation of glycogen synthesis was abolished under these conditions, suggesting that it is secondary to ionic or volume changes. Alkalinization had converse effects on glycolysis and glycogen synthesis. 2. In HCO3(-)-containing media, replacement of NaCl with sodium acetate or potassium acetate, like acidification with CO2, inhibited glycolysis and stimulated glycogen synthesis. The latter correlated with an increase in cation content. Amiloride, an inhibitor of Na+/H+ exchange, inhibited both the increase in cation content and the stimulation of glycogen synthesis, suggesting that the latter is secondary to cell swelling. 3. Hypo-osmotic swelling increased glycogen synthesis in HCO3(-)-containing media, in both the absence and the presence of Na+ and at both 2.5% and 5% CO2, but it increased glycolysis in the presence of Na+ and at 2.5%, but not at 5%, CO2. In HCO3(-)-free media, during acidification and swelling, glycogen synthesis correlated with pH and not with cell volume, indicating that inhibition by acidification over-rides stimulation by swelling. 4. Stimulation of glycolysis by insulin was not additive with stimulation by alkalinization. The stimulation of glycogen synthesis by insulin was partially suppressed under alkaline conditions; it was markedly suppressed in isosmolar Na(+)-free media and restored by hypo-osmotic swelling. In hypo-osmolar Na(+)-free media insulin prevented the decrease in glycogen synthesis with decreasing [HCO3-], suggesting that it counteracts inhibition by acidification. 5. It is concluded that glycogen synthesis and glycolysis are both stimulated by cell swelling and inhibited by acidification, under certain conditions, but glycolysis is more sensitive to inhibition by acidification and glycogen synthesis to stimulation by swelling. Consequently, simultaneous swelling and acidification is associated with inhibition of glycolysis and stimulation of glycogen synthesis. Stimuli that cause swelling and alkalinization activate both glycogen synthesis and glycolysis, alkalinization being more important in control of glycolysis and swelling in control of glycogen synthesis. Both cell swelling and alkalinization are components of the mechanism by which insulin controls glycogen synthesis and glycolysis.

Evidence that a 'memory' for glucose metabolism desensitizes A-cell responsiveness in the perfused pancreas of the rat

1985 ◽  
Vol 110 (1) ◽  
pp. 114-119
Author(s):  
V. Grill ◽  
M. Rundfeldt ◽  
S. Efendić
Keyword(s):  
Glucose Concentration ◽  
Glucagon Secretion ◽  
Energy Availability ◽  
High Glucose Concentration ◽  
Perfused Pancreas ◽  
Total Response ◽  
Cell Sensitivity ◽  
Elevated Glucose ◽  
Cell Energy ◽  
A Cell

Abstract. The effects of prior exposure to glucose or an inhibitor of glycolysis (iodoacetate) on A-cell sensitivity to glucose in the perfused pancreas of the rat was investigated. Inhibition of glucagon secretion by a high glucose concentration (22 mm) was attenuated and delayed when tested 20 min after a previous infusion with the same glucose concentration. Previously elevated glucose also delayed for 2 min a glucagon response to glucose omission whereas the total response was not significantly affected. During a 20 min perfusion with 1 mm iodoacetate, glucagon secretion increased and rates of secretion were further augmented after withdrawal of iodoacetate. When introduced 10 min after cessation of the iodoacetate pulse, 22 mm glucose failed to affect insulin or somatostatin release but, conversely, induced a profound decrease in glucagon secretion which was more marked than during control conditions. Conclusions: A-cell sensitivity to glucose is diminished and enhanced by prior fuel abundance and deprivation, respectively. Such effects could be due to persisting changes in A-cell energy availability rather than to pertubations in insulin or somatostatin secretion.

ÉTUDE IN VITRO DU MÉTABOLISME DES HYDRATES DE CARBONE DANS LE LEUCOCYTE CIRCULANT DU COBAYE TRAITÉ À LA CORTISONE

1966 ◽  
Vol 51 (2) ◽  
pp. 193-202
Author(s):  
J. A. Antonioli ◽  
A. Vannotti
Keyword(s):  
Glucose Concentration ◽  
Intramuscular Injection ◽  
Acute Inflammation ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
List Type ◽  
Hydrates De Carbone

ABSTRACT 1. The metabolism of suspensions of circulating leucocytes has been studied after intramuscular injection of a dose of 50 mg/kg of a corticosteroid (cortisone acetate). The suspensions were incubated under aerobic conditions in the presence of a glucose concentration of 5.6 mm. Glucose consumption, lactate production, and variations in intracellular glycogen concentration were measured. After the administration of the corticosteroid, the anabolic processes of granulocyte metabolism were reversibly stimulated. Glucose consumption and lactate production increased 12 hours after the injection, but tended to normalize after 24 hours. The glycogen content of the granulocytes was enhanced, and glycogen synthesis during the course of the incubation was greatly stimulated. The action of the administered corticosteroid is more prolonged in females than in males. The injection of the corticosteroid caused metabolic modifications which resemble in their modulations and in their chronological development those found in circulating granulocytes of guinea-pigs suffering from sterile peritonitis. These results suggest, therefore, that, in the case of acute inflammation, the glucocorticosteroids may play an important role in the regulation of the metabolism of the blood leucocytes.

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