[The role of Academies of Medicine in the regulation of drug use].
Explore the source record for details and available documents.
Academies and Institutes↗
Biomedical subjects
G Valette
Publications and source records attributed to G Valette.
Structural specificity of nucleotides for insulin secretory action from the isolated perfused rat pancreas.
The study concerned the effects of variuos nucleotides on the insulin secretion from the isolated perfused rat pancreas. ATP, the first nucleotide studied, increased the insulin release induced by glucose 1.5 g/l. There was a first immediate peak followed by a second significant and durable increase. The log dose-response curve was linear for concentrations ranging from 0.825 microM to 330 microM. The effects of natural adenine derivatives (ATP, ADP, 5' AMP, cAMP and adenosine) were compared. ATP was the most active compound; ADP had nearly the same activity as ATP (relative potency ATP/ADP = 3.2); 5' AMP, cAMP and adenosine displayed a very weak activity (about 100 fold less active). Adenylimido-diphosphate (AMP-PNP), a non-phosphorylating structural analogue of ATP, clearly stimulated insulin secretion and its effect was concentration-related. It was about 10 fold less active than ATP. The comparison of triphosphorylated derivatives from various purine nucleosides (ATP, GTP, ITP) or pyrimidine nucleosides (CTP and UTP) showed that only the purine derivatives had a strong insulin secretory effect with, in order of decreasing activity: ATP greater than GTP greater than ITP. These results show that certain structural features (purine basis and di- or triphosphate groups) are essential to elicit an insulin secretory effect.
Adenine Nucleotides↗
Is lactate involved in phenformin-induced insulin secretion?
Phenformin at high doses (10 mg/l, 50 mg/l, and 100 mg/l) increased the insulin and lactate output rates by the isolated perfused rat pancreas. Glucagon secretion was not modified. There was a statistically significant correlation between the increase in insulin and lactate output rates induced by phenformin. Intra-pancreatic L (+) lactate concentrations induced by phenformin were in the range of sodium L (+) lactate concentrations which experimentally stimulated insulin secretion by the same preparation. Thiamin pyrophosphate and sodium dichloroacetate, which promote the aerobic metabolism of pyruvate, opposed the phenoformin induced increase in lactate output by the isolated perfused rat pancreas and provoked as well a decrease in insulin release. These results suggest that the increase in insulin secretion following the administration of phenformin at high concentrations can be explained, to a large extent, by the increase in the production of lactate ions.
Animals↗
Metabolic effects of sodium dichloroacetate in normal and diabetic dogs.
Explore the source record for details and available documents.
Acetates↗
[Tribute to Maurice-Marie Janot, 1903--1978].
Explore the source record for details and available documents.
Chemistry, Organic↗
Evidence for a role of exogenous or endogenous hyperlactatemia in insulin secretion in the dog.
Various types of experimental hyperlactatemia were induced in the normal anesthetized dog, and the changes in insulin secretion were measured in the pancreatico-duodenal vein. Hyperlactatemia was induced in the absence or in the presence of an infusion of sodium dichloroacetate (DCA), which activates pyruvate dehydrogenase. 1. Exogenous hyperlactatemia: The infusion of sodium L(+)lactate resulted in a strong increase in blood lactate level which was accompanied by a significant increase in the insulin output from the pancreatico-duodenal vein. The administration of DCA did not counteract the increase in lactate level and did not modify insulin output either. 2. Endogenous hyperlactatemia: This was induced either by pharmacological means: the subcutaneous injection of an antidiabetic biguanide, phenformin (20 mg/kg), or by physiological means: intense muscular work. In both cases an increase in the lactate level and in insulin output was recorded. The administration of DCA suppressed the hyperlactatemia and counteracted the increase in insulin output. These results show that there is a relationship between lactate level and insulin secretion, and give evidence for a role of endogenous lactate in the regulation of insulin secretion.
Animals↗
[Effects of mescaline and lysergide on the mechanical responses of isolated organs of the rat to catecholamines and the role of calcium transfers in these phenomena].
On isolated Rat vas deferens the contracting responses of noradrenaline and dopamine are increased by mescaline (23 micromoles) and decreased by lysergide (15 micromoles). Similarly, on isolated Rat duodenum previously decalcified the hypertonic responses of recalcification are modified in the opposite direction by the two agonists. On the other hand, mescaline such as lysergide increase the fall of tonus which ensues the decalcification of isolated duodenum.
Animals↗
[Endogenous hyperlactatemia and insulin secretion].
In the normal anesthetized dog, the endogenous hyperlactatemia induced either by intense muscular work or by a high dose of phenformin (20 mg/kg subtucaneously) is followed by an increase in the pancreaticoduodenal insulin output. A previous perfusion of sodium dichloroacetate (50 mg/kg. h) opposes the hyperlactatemia, and reduces or suppresses the increase in insulin output.
Animals↗
[Sodium dichloracetate: its application to the therapeutics of experimental hyperiactatemia (author's transl)].
Different types of experimental hyperlactatemia and hyperpyruvicemia with or without lowering of blood pH were induced in anesthetized dogs. The initially studied experimental model was the hyperlactatemia and hyperpyruvicemia with lowering of blood pH induced by the intraduodenal administration of high doses of phenformin. Intravenous perfusion of sodium dichloroacetate (150 mg/kg infused during 20 minutes), which acts on the enzymatic complex of pyruvate dehydrogenase, reduced the hyperiactatemia and hyperpyruvicemia with or without acidosis provoked by phenformin injected intraduodenally (30 mg/kg), by intense muscular work, by hypoxia or by continous perfusion or adrenaline. Exogenous or endogenous insulin combined with sodium dichloracetate reduced the hyperlactatemia and hyperpyruvicemia as well as the changes in blood pH provoked by phenformin, more strongly than did sodium dichloroacetate alone. These findings have been confirmed in the conscious dog.
Acetates↗
[The effect of alkaloids from Tabernanthe iboga H. Bn. on the response of isolated organs to catecholamines and the possible role of calcium exchange. Case of Ibogaine].
On isolated Rat duodenum, ibogaine (70 mumoles/l) increases the hypertonic effect following the addition of Calcium ions to the organ previously decalcified. Moreover, this alkaloid increases the hypotomic effect resulting from decalcification of the normal organs. These actions are taken into account with the potentiating effects of ibogaine on noradrenaline and dopamine responses observed on rat vas deferens.
Alkaloids↗
[Effects of Tabermanthe iboga H. Bn. alkaloids on the isolated organ responses to catecholamines and the role of calcium exchanges. Tabernanthine].
Using isolated Rat duodenum previously decalcified, the authors have investigated the effect of tabernanthine on the increase of tonus brought about by addition of calcium ions at different concentrations. The observed potentiating effect of tabernanthine towards the calcium responses may be pointed out concerning the mechanism of sensitizing effect of this alkaloid on the responses of isolated organs to catecholamines such as noradrenaline and dopamine.
Alkaloids↗
[Reduction by sodium dichloroacetate and by insulin of the severe hyperlactemia following phenformin administration in anesthetized or awake dogs].
Explore the source record for details and available documents.
Acetates↗
[Effects of thiamine pyrophosphate and sodium dichloroacetate on the increase of lactate and insulin outputs induced by phenformin on the isolated and perfused rat pancreas].
Thiamine pyrophosphate and sodium dichloroacetate, substances which promote the aerobic metabolism of pyruvate, reduce the increase in lactate output induced by phenformin (100 mg/l) on the isolated and perfused rat pancreas. Both substances provoke a decrease in insulin secretion produced by phenformin.
Acetates↗
[Adenosine triphosphate (ATP) and insulin secretion: effect of different concentrations and effect of temperature].
In the presence of a glucose concentration of 1.5 g/1, ATP provokes a biphasic stimulation of insulin secretion from the isolated and perfused rat pancreas. For ATP concentrations ranging from 0.5 mg/1 to 200 mg/1, the increase in insulin secretion presents a linear relation with the logarithm of the concentration. Lowering the temperature from 37.5 degrees C to 28 degrees C provokes a decrease in insulin secretion induced by glucose (1.5 g/1). In response to the stimulation by ATP, the increase in insulin secretion measured during the first phase is weaker at 28 degrees C than at 37.5 degrees C when estimated in ng/min; however, when evaluated in percentage in relation to the baseline value, this increase is more important at the lower temperature.
Adenosine Triphosphate↗
[Lack of concordance in the effect of large doses of phenformin on insulin secretion and glycemia. Tentative analysis].
In the anesthetized dog normal or pretreated with phenformin (20 mg/kg per os) for 7 days, a subcutaneous injection of this biguanide (20 mg/kg) triggers a considerable hyperinsulinemia without concomitant hypoglycemia. The insulin secreted by these animals is biologically active on rat epididymal fat pads. On the other hand, epididymal fat pads of rats pretreated with phenformin display a lower response to insulin than that of non treated rats. The hypoglycemic effect of the same dose of insulin is less important in the normal dog after chronic pretreatment with phenformin.
Adipose Tissue↗
[Actions of sodium dichloroacetate in combination with insulin on hyperlactatemia and hyperpyruvicemia induced in dogs by phenformin].
In the normal anesthetized dog the combination of insulin, whether of exogenous or endogenous origin, with sodium dichloroacetate provoke a rapid and important reduction of the hyperlactatemia and hyperpyruvicemia induced by the intraduodenal injection of high doses of phenformin. Furthermore this combination prevents the progressive and important lowering of the arterial pH provoked by phenformin.
Acetates↗