Calcium and pancreatic β-cell function I. Stimulatory effects of pentobarbital on insulin release

doi:10.1016/0304-4165(77)90297-5

Biochimica et Biophysica Acta (BBA) - General Subjects

Volume 497, Issue 3, 26 May 1977, Pages 766-774

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Abstract

Islets microdissected from ob/ob-mice were exposed to 3mM pentobarbital in media which were normal or deficient in Ca²⁺. This treatment resulted in a marked decrease of the islet content of cyclic AMP recorded in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Pentobarbital had a dual effect on insulin release. In addition to being a potent inhibitor of glucose-stimulated insulin release in media containing 2.56 mM Ca²⁺ it increased the amounts of insulin released in high glucose media deficient in Ca²⁺. There was a transient stimulation with ordinary concentrations of Ca²⁺ and 3 mM glucose when the media also contained 3-isobutyl-1-methylxanthine. The stimulatory effect of pentobarbital persisted after replacing part of the Ca²⁺ in the β-cell membrane with lanthanum ions and it could not be mimicked by lowering the oxygen tension of the incubation medium. It is suggested that pentobarbital stimulation of insulin release is the result of a specific action of the drug on the distribution of Ca²⁺ within the pancreatic β-cells.

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Effect of repeated sodium pentobarbitone administration on glucose homeostasis in mice
1980, General Pharmacology
1. Glucose tolerance tests were conducted in conscious and pentobarbitone-anaesthetized mice after daily administration of an anaesthetic dose of sodium pentobarbitone (45 mg/kg) for 10 consecutive days.
2. Mice examined in the conscious state showed impaired glucose tolerance and reduced plasma insulin concentrations compared with conscious controls.
3. Mice examined in the anaesthetized state also showed reduced insulin concentrations, although glucose tolerance was not significantly altered in comparison with anaesthetized controls.
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5. The results demonstrate that 10 consecutive daily treatments with an anaesthetic dose of pentobarbitone impair glucose homeostasis and lower plasma insulin concentrations in mice.
Calcium and pancreatic β-cell function. 6. glucose and intracellular <sup>45</sup>Ca distribution
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Calcium and pancreatic β-cell function. 4. Evidence that glucose and phosphate stimulate calcium-45 incorporation into different intracellular pools
1978, BBA - General Subjects
β-Cell-rich pancreatic islets were microdissected from ob/ob-mice and used for studies of ⁴⁵Ca uptake and washout. Irrespective of whether the experiments were performed at 21 or 37°C both glucose and phosphate stimulated the net uptake of lanthanum-nondisplaceable ⁴⁵Ca. The stimulatory effect of phosphate was additive to that produced by glucose. ⁴⁵Ca incorporated in response to phosphate differed from that taken up in the presence of 20 mM glucose in being easily washed out although it was not affected by the glucose concentration of the washing medium. The efflux of ⁴⁵Ca was reduced after introducing phosphate into a medium used to perifuse islets which had accumulated ⁴⁵Ca in response to 20 mM glucose. This suggests that the outward calcium transport can be influenced also by intracellular trapping of the cation. The glucose-stimulated insulin release was inhibited by phosphate; an effect reversed by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. It is concluded that a common effect of glucose and phosphate is to trap calcium in the pancreatic β-cells but that there are fundamental differences between their effects on intracellular distribution of calcium and on insulin release.
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Calcium and pancreatic β-cell function I. Stimulatory effects of pentobarbital on insulin release

Abstract

Biochim. Biophys. Acta

Anal. Biochem.

FEBS Lett.

Biochem. Pharmacol.

FEBS Lett.

Endocrinology

Ann. N.Y. Acad. Sci.

Diabetologia

Acta Endocrinol.

Endocrinology

Endocrinology

Endocrinology