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Adaptive short-term associative conditioning in the pancreatic β-cell

par Sanchez-Andres, J.V.;Pomares, Raquel;Malaisse, Willy
Référence Physiological Reports, 8, 6, e14403
Publication Publié, 2020-03

Article révisé par les pairs

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Résumé :

This study associates cholinergic stimulation of the pancreatic β-cell electrical activity with a short-term memory phenomenon. Glucose pulses applied to a basal glucose concentration induce depolarizing waves which are used to estimate the evolution of the β-cell glucose sensitivity. Exposure to carbamoylcholine (carbachol) increases the size of the glucose-induced depolarizing waves. This change appears after carbachol withdrawal and implies a temporal potentiation of sensitivity (TPS) lasting up to one hour. TPS induction requires the simultaneous action of carbachol and glucose. The substitution of glucose with the secretagogues glyceraldehyde or 2-ketoisocaproate mimics glucose-induced TPS, while palmitate does not. TPS is not produced if the membrane is kept hyperpolarized by diazoxide. Glucose can be replaced by tolbutamide, suggesting a role of depolarization and a subsequent increase in intracellular calcium concentration. A role for kinases is suggested because staurosporine prevents TPS induction. Cycloheximide does not impair TPS induction, indicating that de novo protein synthesis is not required. The fact that the two inputs acting simultaneously produce an effect that lasts up to one hour without requiring de novo protein synthesis suggests that TPS constitutes a case of short-term associative conditioning in non-neural tissue. The convergence of basal glucose levels and muscarinic activation happens physiologically during the cephalic phase of digestion, in order to later absorb incoming fuels. Our data reveals that the role of the cephalic phase may be extended, increasing nutrient sensitivity during meals while remaining low between them.