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  • 1
    ISSN: 1432-0428
    Keywords: Acyl-amino-alcyl benzoic acid derivative ; hypoglycaemic agent ; insulin release ; pancreatic polypeptide ; glucagon ; somatostatin ; tolbutamide ; unanaesthetized dogs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of HB 699, a non-sulphonyl urea acyl-amino-alcyl benzoic acid derivative, were studied in unanaesthetized dogs. Changes in blood glucose and plasma insulin, glucagon, pancreatic polypeptide and somatostatin were measured after a single intravenous injection. HB 699 caused hypoglycaemia and stimulated insulin secretion in a dosedependent manner. The effects of HB 699 (40 mg/ kg) on pancreatic hormone secretion were compared to those of tolbutamide given at a dose (12 mg/kg) which induced a similar maximal hypoglycaemia. Both drugs caused a similar increase in insulin release (180±32% for tolbutamide and 240±41% for HB 699) lasting for approximately 1 hour. Despite hypoglycaemia, plasma glucagon concentrations were unaltered by either substance. HB 699 caused a marked increase in the secretion of pancreatic polypeptide (220±60% at 30 min) for up to 2 hours, whereas tolbutamide caused no significant change in plasma pancreatic polypeptide levels. In contrast, while tolbutamide caused a significant (45±12%) but short-lived increase in plasma somatostatin concentrations, HB 699 had no significant effect.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Benzothiadiazine analogue ; LN 5330 ; diazoxide ; glucagon ; insulin ; somatostatin secretion ; dog ; isolated perfused rat pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary LN 5330 is a new benzothiadiazine which is a structural analogue of diazoxide. Its effects in vivo were studied on blood glucose levels and insulin, glucagon and somatostatin secretion in normal dogs, and in vitro on glucagon and insulin secretion from the isolated perfused rat pancreas. The results were compared with those obtained with diazoxide at equimolar dose or concentration. In the normal anaesthetized dog having a T-shaped catheter inserted in the pancreaticoduodenal vein, the infusion of LN 5330 (87.8 μmol/kg for 20 min) induced (1) a progressive increase in blood glucose levels, (2) a rapid decrease in insulin and somatostatin output rate, (3) an immediate increase in pancreatic glucagon secretion, and (4) a delayed decrease of arterial blood pressure. The equimolar dose of diazoxide provoked the same effects on blood glucose levels, insulin and somatostatin output, but a marked decrease in glucagon output and in arterial blood pressure. In the isolated rat pancreas perfused with 8.3 mmol/l glucose, the infusion of LN 5330 (440 μmol/l for 30 min) induced a drastic fall in insulin and a rapid and persistent increase in glucagon output. This stimulatory effect on glucagon secretion was not found with diazoxide at equimolar concentration. These findings show that LN 5330 is a substance which is distinct from diazoxide and interesting because of its double action: inhibition of insulin secretion and stimulation of glucagon secretion.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Insulin secretion ; adrenaline ; noradrenaline ; catecholamines ; dog ; blood glucose ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of adrenaline and noradrenaline infusions on pancreaticoduodenal venous insulin output were studied in anaesthetized normal dogs. Two experimental protocols were used. In the first, the dogs had a normal blood glucose level at the start of the catecholamine infusion (normoglycaemic dogs). In the second, the animals were made hyperglycaemic by a continuous glucose infusion (hyperglycaemic dogs). In the normoglycaemic dogs, adrenaline (0.5 μg · kg-1 · min-1) provoked hyperglycaemia accompanied by an increase in insulin output. Noradrenaline (0.5 μg · kg-1 · min-1) also caused an increase in insulin output but without any significant change in blood glucose. In hyperglycaemic dogs, adrenaline (2 μg · kg-1 · min-1) reduced the insulin response and enhanced the hyperglycaemia; noradrenaline (2 μg · kg-1 · min-1) markedly increased the insulin response (+ 2250%) without any significant change in blood glucose. Propranolol (0.3 mg/kg, IV) prevented the increase of insulin induced by noradrenaline. These findings show that, in the normal dog, adrenaline and noradrenaline infusions can produce opposite effects on insulin response depending on the experimental conditions.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1439-6327
    Keywords: 2-Chloropropionate ; Force-velocity test ; Anaerobic power ; Venous plasma lactate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the effects of a stimulation of pyruvate dehydrogenase (PDH) activity induced by 2-chloropropionate (2-CP) on venous plasma lactate concentration and peak anaerobic power (W an, peak) during periods (6 s) of incremental intense exercise, i.e. a force-velocity (F-ν) test known to induce a marked accumulation of lactate in the blood. TheF-ν test was performed twice by six subjects according to a double-blind randomized crossover protocol: once with placebo and once with 2-CP (43 mg · kg−1 body mass). Blood samples were taken at ingestion of the drug, at 10, 20, and 40 Min into the pretest period, at the end of each period of intense exercise, at the end of each 5-min recovery period, and after completion of theF-ν test at 5, 10, 15, and 30 min. During theF-ν test, venous plasma lactate concentrations with both placebo and 2-CP increased significantly when measured at the end of each period of intense exercise (F = 33.5,P 〈 0.001), and each 5-min recovery period (F = 24.6,P 〈 0.001). Venous plasma lactate concentrations were significantly lower with 2-CP at the end of each recovery period (P 〈 0.01), especially for high braking forces, i.e. 8 kg (P 〈 0.05), 9 kg (P 〈 0.02), and maximal braking force (P 〈 0.05). After completion of theF-ν test, venous plasma lactate concentrations were also significantly lower with 2-CP (P 〈 0.001). The percentage of lactate decrease between 5- and 30-min recovery was significantly higher with 2-CP than with the placebo [59 (SEM 4)% vs 44.6 (SEM 5.5)%,P 〈 0.05]. Furthermore,W an, peak was significantly higher with 2-CP than with the placebo [1016 (SEM 60) W vs 957 (SEM 55) W,P 〈 0.05]. In conclusion, PDH activation by 2-CP attenuated the increase in venous plasma lactate concentration during theF-ν test. Ingestion of 2-CP led to an increasedW an, peak.
    Type of Medium: Electronic Resource
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