Biomedical subjects
Publications and source records attributed to A L Loubatières.
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.
Lowering of the temperature from 37.5 degrees C to 28 degrees C provokes a decrease in the response of the beta cell to the stimulation by glucose (1.5 g/1, 3 g/1 and 5 g/1). The insulin secretion obtained at 28 degrees C, compared to that obtained at 37.5 degrees C, is weaker for strongly stimulating concentrations (3 g/1 and 5 g/1) than for a slightly stimulating concentration (1.5 g/1).
In the normal anesthetized dog a continuous perfusion of sodium dichloroacetate (30 mg/kg.h) prevents the increase in blood lactates and pyruvates as well as the lowering of the arterial pH induced by the intraduodenal administration of phenformin (30 mg/kg). Furthermore a perfusion of sodium dichloroacetate (7.5 mg/kg.mn) during 20 minutes, three hours after the administration of phenformin, tends to improve the utilization of blood lactates and pyruvates.
On the isolated perfused rat pancreas phenformin at high concentrations (10 mg/1, 50 mg/1 and 100 mg/1) provokes an increase of the insulin and lactate output in the effluent liquid. In no case is glucagon secretion modified by this substance. There exists a statistically significant correlations between the increase in insulin output and the increase in lactate output induced by phenformin.
ATP stimulates glucagon and insulin secretions from the isolated perfused rat pancreas. This effect is modulated by glucose. Glucagon secretion is stimulated by ATP only in the absence or in the presence of a low glucose concentration (0.5 g/1). As to insulin secretion, it is strongly stimulated only in the presence of a glucose concentration of 1.5 g/1.
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The chronic oral administration of phenformin (20 mg/kg daily during 8 days) to the normal concious dog provokes a decrease in the fasting thiamine levels of plasma and erythrocytes. During intragastric loading tests with thiamine hydrochloride (30 mg/kg), carried out during the chronic treatment with the biguanide, the curve of plasma hyperthiaminemia is increased. The authors suggest an explanation for these apparently contradictory results.
Glibenclamide stimulates the insulin secretion by the isolated and perfused rat pancreas, but does not inhibit glucagon secretion when the perfusion liquid contains 1.5 g/I glucose. In the absence of glucose in the perfusion medium, glibenclamide stimulates both insulin and glucagon secretions.
In the normal anesthetized dog, a cocarboxylase perfusion considerably reduced the increase in blood lactate and pyruvate levels provoked by the intraduodenal injection of phenformin (30 mg/kg); furthermore it seems to counteract the increase of the lactates/pyruvates ratio and opposes the fall in blood pH.
Glipizide is a new hypoglycaemic sulphonylurea. In this work we have studied experimentally the hypoglycaemic activity of this drug, its insulin secretory effect and its action on the development of the islets of Langerhans. Studies in the dog: In the normal conscious dog the hypoglycaemic effect of the drug was studied when increasing doses (0,03 mg/kg, 0,05 mg/kg, 0,07 mg/kg and 0,09 mg/kg) were injected intravenously. The hypoglycaemic effect of the drug occurred rapidly, reaching a maximum in about 30 minutes. The relative potency of glipizide was determined in comparison with tolbutamide. Under our experimental conditions, glipizide proved to be on average 99 times more active than tolbutamide when the doses were evaruated by weight; when the doses were expressed in moles it was 163 times more active. Plasma insulin levels manifested an increase at the first minute. This rose rapidly to a maximum at 5 to 15 minutes after the injection. Following this, insulinemia decreased and the values recorded at 60 minutes were about the same as the starting values. There is a linear relation between the logarithm of the dose and the area under the insulin curve measured for the first sixty minutes. After oral administration to the normal dog, glipizide (081 mg/kg and 1mg/kg) provoked a hypoglycemia manifested after a 30 to 60 minutes latent period. With the dose of 1 mg/kg the maximal effect on blood glucose level was reached between 1,30 and 3 hours, depending on the animal. Plasma insulin levels also increased after a latent period which varied from one animal to another. The dogs presenting the earliest increase in insulinemia were those in which glycemia drops most rapidly. Comparison with other sulfonamides (glibenclamide, glisoxepide and tolbutamide) showed that the hypoglycemic action of glipzide was very similar to that of glisoxepide and that it occurred much earlier than with glibenclamide. The insulin secretory effect of glipizide also occurred much earlier than that of glibenclamide, manifesting itself as early as that of glisoxepide and tolbutamide. Studies on the isolated rat pancreas: On the isolated rat pancreas perfused with Krebs-Ringer solution containing glucose (1,5 g/l), glipizide (10 mug/I) considerably increased the amount of secreted insulin. The stimulation of insulin secretion occurred rapidly and persisted powerfully during the entire duration of the infusion. It faded out progressively after stopping the infusion and the secretion remained higher than the control secretion during the following 45 minutes of the experiment. A concentration as low as 0,5 mug/I provoked a distinct increase of insulin secretion. Studies on the development of the islets of langerhans in the mouse: The prolonged administration of glipizide (100 mg/kg daily for 35 days) increased the "insular index", which is directly proportional to the islet weight, by 27%. Therefore this product possesses betacytotrophic activity...
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