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G Devis

Publications and source records attributed to G Devis.

31 records · Page 2Linked to original sources
PubMed1976

Calcium-antagonists and islet function. VI. Effects of barium.

The modality of Ba2+-induced insulin release was investigated in the isolated perfused rat pancreas. The insulinotropic action of Ba2+ was antagonized by Ca2+, Mg2+ and verapamil, and enhanced by EGTA, theophylline, glucose and cytochalasin B. Likewise the net uptake of 133Ba2+ by isolated islets was inhibited by Ca2+, Mg2+ and verapamil. Glucose increased 133Ba2+ net uptake, but only when sufficient Ba2+ had accumulated in the islets. Theophylline failed to affect 133Ba2+ net uptake. These data suggest that (i) Ba2+-induced insulin release is dependent on the accumulation of this cation in the B-cell; (ii) Ba2+ inward transport in the B-cell occurs through a verapamil-sensitive channel characterized by competition between Ba2+, Ca2+ and Mg2+; and (iii) the enhancing effect of theophylline upon insulin release could be due to an intracellular translocation of alkaline-earth cations rather than to an increase in their net uptake. The present findings also support the idea that insulin release can be triggered by the accumulation of suitable divalent cations in a critical site of the B-cell, leading to the activation of a cytochalasin B-response effector system.

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PubMed1976

Calcium-antagonists and islet function. IV. Effect of D600.

D600 (2 to 20 muM; alpha-isopropyl-alpha [(N-methyl-N-homoveratril)-gamma-aminopropyl]-3,4,5-trimethoxyphenyl-acetonitril) caused a dose-related, rapid and reversible inhibition of glucose-induced insulin release. It also suppressed the insulinotropic action of a sulphonylurea but failed to affect the enhancing action of theophylline upon glucose-induced release. The inhibitory effect of D600 was enhanced at low extracellular Ca2+ concentration. D600 reduced both basal and glucose-stimulated 45calcium net uptake, whilst failing to affect the efflux of 45calcium from perifused islets. The recognition of glucose by the B-cell was also unaffected by D600 as judged by the effect of the sugar upon both 45calcium efflux and net uptake in the isolated islets. These findings are compatible with the hypothesis that the primary mode of action of D600 is to inhibit Ca2+ entry in the B-cell.

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PubMed1976

Calcium-antagonists and islet function. V. Effect of R33711.

R33711, a new drug with presumed potent calcium-antagonistic property, was found to suppress the insulinotropic action of glucose and gliclazide but not that of theophylline. A 0.2 muM concentration of R33711 was sufficient to abolish glucose-induced insulin release. At this concentration, R33711 inhibited the net uptake of 45Ca2+ by isolated islets, whether in the absence or presence of either glucose or sulfonylurea. In the isolated islets, R33711 failed to affect the glucose-stimulated production of lactate, the rate of 45Ca2+ efflux, the inhibitory action of glucose upon such an efflux and its increase in response to theophylline. These data are compatible with the view that R33711 inhibits entry of Ca2+ into the B-cell and that integrity of such an inward cationic movement usually plays a permissive role in the maintenance of the Ca2+-dependent insulin secretory process.

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PubMed1976

Calcium antagonists and islet function. II. Interaction of theophylline and verapamil.

Verapamil inhibits glucose-induced insulin release by the isolated perfused rat pancreas. The dose-response relationship for the inhibitory action of verapamil is shifted to higher concentrations of the drug when the concentration of calcium in the perfusate is increased. The degree of inhibition of glucose-induced insulin release by a given concentration of verapamil decreases as the length of exposure to glucose is increased prior to introduction of the calcium antagonist. Theophylline augments glucose-stimulated insulin release and protects the beta-cell against the inhibitory action of verapamil, both effects of theophylline being dose-related. Even after pretreatment of the pancreas with a high concentration of verapamil, theophylline is able, in the presence of glucose, to stimulate insulin release and, eventually, to restore a nearly normal secretory response to this sugar. We suggest that theophylline, by mobilizing calcium from an organelle-bound pool within the beta-cell, compensates for the verapamil-induced reduction in calcium inward transport into the beta-cell.

Animals↗
PubMed1976

Calcium antagonists and islet function. VIII. The effect of magnesium.

Mg2+ in high concentration (10 to 20 mEq/l) caused a dose-related inhibition of glucose-induced 45calcium net uptake and subsequent insulin release in isolated islets. Experiments performed with the isolated perfused pancreas indicated that the inhibitory effect of Mg2+ upon insulin secretion was rapid and reversible. Although excess Mg2+ reduced lactate production by the islets, the process of glucose recognition by the B-cell was apparently unaltered as judged by the inhibitory effect of the hexose upon 45calcium efflux from perifused islets and the resultant accumulation of 45calcium in the islets. Mg2+ in high concentration failed to facilitate 45calcium efflux from the islets, whether in the presence or absence of glucose. These data suggest that the major effect of Mg2+ upon islet function is to inhibit Ca2+ entry in the B-cell.

Animals↗
PubMed1975

Dynamics of insulin release and microtubular-microfilamentous system. VII. Do microfilaments provide the motive force for the translocation and extrusion of beta granules?

The active role played by beta-cell microfilamentous structures in the dynamics of insulin secretion was investigated by examining the influence of cytochalasin B upon various parameters of hormonal release by the isolated perfused rat pancreas. The view that the cytochalasin-induced changes in insulin release are due to a primary biophysical effect on microfilaments, rather than to an unrelated biochemical alteration of the beta-cell glucose-sensor device, was strengthened by the following observations: (1) the onset and disappearance of the cytochalasin B-induced facilitating action upon insulin release followed a time-course parallel to that characterizing the ultrastructural changes provoked by the drug in the distribution of beta-cell microfilamentous material; and (2) cytochalasin B facilitated leucine-induced insulin release in the presence of a very low glucose concentration. The mold metabolite was also found to transform transient secretory responses into biphasic ones and to prevent the reduction that normally affects the early response to insulinotropic agents when the pancreas is stimulated a few minutes after a prior and short exposure to glucose. The release of insulin evoked by either glucose or gliclazide was abolished in the absence of extracellular calcium, whether in the presence or absence of cytochalasin B. Theophylline and cytochalasin B exerted a synergistic effect upon glucose-induced insulin release. These data support the concept that calcium-dependent contractile events involving cytochalasin B-sensitive microfilamentous structures provide the motive force for both the intracellular translocation and exocytotic release of beta granules.

Animals↗
PubMed1975

Calcium antagonists and islet function. I. Inhibition of insulin release by verapamil.

Verapamil is a potent calcium antagonist known to inhibit excitation-contraction coupling in both myocardium and myometrium. Its effect upon glucose- and sulfonylurea-induced insulin release was investigated in the isolated perfused rat pancreas. After twenty-five minutes' pretreatment and at concentrations ranging between 0.8 and 8.1 muM, verapamil caused a dose-related inhibition of glucose-induced insulin release during both the early and late phase of the secretory process. At a concentration of 0.8 muM, the degree of inhibition was more marked when the exposure time to verapamil prior to stimulation with glucose was increased to sixty minutes. Verapamil also inhibited gliclazide-induced insulin release. Infusion of verapamil during the late phase of the secretory response to glucose demonstrated that the inhibition of insulin release was an immediate and reversible phenomenon. The inhibitory effect of verapamil was enhanced at a subnormal calcium concentration and reduced at a high calcium concentration. These findings are consistent with the well-known calcium dependency of both glucose- and sulfonylurea-induced insulin release and suggest that verapamil might be a promising tool for further studies on the interactions between cations and secretagogues in the beta-cell secretory process.

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PubMedDate not supplied

Calcium antagonists and islet function. IX. Is extracellular calcium required for insulin release?

The physiological relevance of extracellular Ca2+ and Mg2+ to the process of glucose-induced insulin release is examined in both the isolated perfused rat pancreas and rat isolated pancreatic islets. When no Ca2+ is added to the perfusion or incubation media, both the initial and late phases of insulin release are severely impaired. The effect of Ca2+ deprivation is an immediate and immediately reversible phenomenon, although the length of the period of Ca2+ deprivation prior to stimulation with glucose modulates the severity of the impairment in the secretory response. When Mg2+ is omitted from the media, the response to glucose occurs precociously and at a higher than normal rate, such a facilitation being a rapid phenomenon. When both Ca2+ and Mg2+ are removed from the extracellular milieu, the secretory response may occur in a normal fashion, except for an earlier onset. The rate of secretion is only reduced after or during a prolonged exposure of the endocrine pancreas to media deprived of both Ca2+ and Mg2+. The release of insulin evoked by glucose in the absence of Ca2+ and Mg2+ is enhanced by theophylline, partially inhibited by verapamil, and abolished by the Ca2+-chelator EGTA. It is concluded that Mg2+, in physiological concentration, exerts an inhibitory effect upon the process of glucose-induced insulin release. However, even in the absence of extracellular Mg2+, the secretory process remains apparently dependent on the availability of minute amounts of extracellular Ca2+.

Animals↗
PubMedDate not supplied

The stimulus-secretion coupling of glucose-induced insulin release XIX. The insulinotropic effect of glyceraldehyde.

Glyceraldehyde is known to stimulate insulin release. Its influence on various parameters of islet function was investigated in order to assess the possible significance of glycolsis in the insulinotropic action of glucose. In the absence of glucose, glyceraldehyde (5-20 mM), but neither dihydroxyacetone nor glycerol stimulated insulin release in rat isolated islets. The glucose-like effect glyceraldehyde (10 mM) was characterized by a shift to the left of the curve relating insulin release to glucose concentration, without any significant increase in the maximal velocity of the secretory process. In the isolated perfused rat pancreas, glyceraldehyde provoked a biphasic secretory response. Glyceraldehyde-induced insulin release was inhibited in the absence of calcium or in the presence of epinephrine, unaffected by mannoheptulose or 3,3-tetramethyleneglutaric acid, and enhanced by theophylline and cytochalism B. Glyceraldehyde also stimulated to pro-insulin biosynthesis and 45Ca net uptake by isolated islets, the latter effect being apparently due, in part at least, to inhibition of calcium outward transport across the cell membrane. At concentrations of nearly equivalent insulinotropic potency, glucose and glyceraldehyde were metabolized at rates yielding comparable output of both lactate and 14CO2. The data indicate that glyceraldehyde mimics many effects of glucose on islet function, suggesting that the insulinotropic action of glucose may be related to its metabolism through the glycolytic pathway.

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