Distinct effects of acetylcholine and glucose on <sup>45</sup>calcium and <sup>86</sup>rubidium efflux from mouse pancreatic islets

Nenquin, Myriam; Awouters, P.; Mathot, Frédéric; Henquin, Jean‐Claude

doi:10.1016/0014-5793(84)81218-1

Cited by 42 publications

(28 citation statements)

References 21 publications

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“…This postulated effect of CCK-8S was observed whether or not insulin secretion was augmented. A similar dissociation of Ca 2+ efflux and insulin release has been previously noted with both carbachol and acetylcholine and seems to indicate that events in addition to Ca 2+ mobilization are required for these agonists to induce either an initial or sustained secretory response (35)(36)(37).…”

Section: Discussionsupporting

confidence: 52%

Interactions of Cholecystokinin and Glucose in Rat Pancreatic Islets

Zawalich

Takuwa

et al. 1987

Diabetes

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The effects of sulfated cholecystokinin (CCK-8S) and glucose on insulin secretion and polyphosphoinositide (PPI) metabolism were studied in isolated rat islets. Both agonists stimulate PPI hydrolysis, inositol phosphate accumulation, 3H efflux from [3H]inositol-prelabeled tissue, and 45Ca efflux from prelabeled cells. However, the effects of CCK-8S on PPI metabolism are considerably greater than those of glucose. Furthermore, the effects of CCK-8S on PPI and Ca2+ metabolism are observed whether islets are incubated in either 2.75 or 7 mM glucose, but CCK-8S only stimulates insulin secretion (a biphasic response) when the higher glucose concentration is present. Addition of 1 microM forskolin to islets incubated in media containing 2.75 mM glucose does not influence basal insulin secretion but sensitizes the islets to the action of CCK-8S. In the presence of forskolin, CCK-8S induces a very marked first phase but no second phase of insulin secretion. We postulate that CCK-8S acts in this tissue via receptor-linked PPI hydrolysis, leading to an inositol trisphosphate-induced Ca2+ efflux. These receptor-mediated effects of CCK-8S are not altered either by the ambient glucose concentration or the cAMP content of the islets, but these two factors determine the responsiveness of the islets (in terms of insulin secretion) to a given CCK-8S signal.

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Section: Discussionsupporting

confidence: 52%

Interactions of Cholecystokinin and Glucose in Rat Pancreatic Islets

Zawalich

Takuwa

et al. 1987

Diabetes

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“…Blockade of Padrenoceptors by propranolol did not prevent the response to 1-adamantanamine. Activation, not inhibition, of muscarinic receptors in P-cells increases insulin release (Nenquin et al, 1984). Incidentally, antimuscarinic effects of I -adamantanamine on P-cells must be very weak, if present, since 100 pM of the drug did not affect the response to I pLM acetylcholine (unpublished observations).…”

Section: Effects Ofvarious Adamantane Derivativesmentioning

confidence: 89%

Adamantane derivatives: a new class of insulin secretagogues

Garrino¹,

Henquin

1987

British J Pharmacology

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1 Adamantane derivatives were found to increase insulin release in vitro. Mouse islets were used to study the mechanisms and molecular requirements of that hitherto unrecognised property.2 At a non-stimulatory concentration of glucose (3mM), 1-adamantanamine (1 mM) reversibly inhibited`6Rb efflux from islet cells, depolarized the P-cell membrane, induced electrical activity, stimulated 45Ca uptake and efflux, and triggered insulin release. Omission of extracellular Ca2" abolished the secretory response but only partially inhibited the acceleration of 45Ca efflux.3 At a stimulatory concentration of glucose (10 mM), 1-adamantanamine reversibly increased '8Rb efflux, potentiated electrical activity (lengthening of the slow waves with spikes), augmented 45Ca uptake and efflux, and increased insulin release. The effects of adamantanamine were dose-dependent, with a threshold concentration of 1O iM for stimulation of release. 4 2-Adamantanamine was as potent as l-adamantanamine. In contrast, substitution of the amino group by a carboxyl group (l-adamantanecarboxylic acid) decreased the effectiveness by about 65%, and substitution by a hydroxyl group (1-adamantanol) suppressed it.

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“…In the present study carbachol had opposite effects to glucose in promoting the efflux of calcium during perifusion of islets with a Ca2+-deficient medium. Recordings of the 86Rb efflux revealed the existence of striking differences in the ionic effects of muscarinic receptor activation and exposure to glucose also with regard to the membrane permeability of K+ [36,37], It is possible to envisage a number of mechanisms by which muscarinic stimula tion of the polyphosphoinositide breakdown may initiate prompt mobilization of a dis tinct pool of calcium in the pancreatic p-cells. The rapid response to carbachol is.…”

Section: Discussionmentioning

confidence: 99%

Mobilization of Different Intracellular Calcium Pools after Activation of Muscarinic Receptors in Pancreatic Beta-Cells

Hellman

Gylfe²

1986

Pharmacology

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Exposure to carbachol resulted in a biphasic stimulation of ⁴⁵Ca efflux when β-cell-rich pancreatic islets from ob/ob mice were perifused with a Ca²⁺-deficient medium. The pattern of stimulated 45Ca efflux was markedly modified by glucose. Whereas the initial carbachol-stimulated phase was conditional on previous exposure to glucose, the subsequent phase was completely suppressed by 20 mmol/l of the sugar. The stimulatory phases could be clearly separated also on the basis of a Na⁺ dependence. Removal of extracellular Na⁺ resulted in a disappearance of the second phase, but it was still possible to induce a prominent initial peak if depletion of intracellular K⁺ was prevented when Na⁺ was omitted. It is concluded that activation of muscarinic receptors in the pancreatic β-cells results in mobilization of calcium from more than one intracellular pool. Whereas the second phase of stimulated efflux can be explained in terms of an increased entry of Na⁺ into the β-cells, the initial stimulation may be due to receptor-mediated breakdown of polyphosphoinositides.

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Distinct effects of acetylcholine and glucose on ⁴⁵calcium and ⁸⁶rubidium efflux from mouse pancreatic islets

Cited by 42 publications

References 21 publications

Interactions of Cholecystokinin and Glucose in Rat Pancreatic Islets

Interactions of Cholecystokinin and Glucose in Rat Pancreatic Islets

Adamantane derivatives: a new class of insulin secretagogues

Mobilization of Different Intracellular Calcium Pools after Activation of Muscarinic Receptors in Pancreatic Beta-Cells

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Distinct effects of acetylcholine and glucose on 45calcium and 86rubidium efflux from mouse pancreatic islets

Cited by 42 publications

References 21 publications

Interactions of Cholecystokinin and Glucose in Rat Pancreatic Islets

Interactions of Cholecystokinin and Glucose in Rat Pancreatic Islets

Adamantane derivatives: a new class of insulin secretagogues

Mobilization of Different Intracellular Calcium Pools after Activation of Muscarinic Receptors in Pancreatic Beta-Cells

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Product

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Distinct effects of acetylcholine and glucose on ⁴⁵calcium and ⁸⁶rubidium efflux from mouse pancreatic islets