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

Abstract

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.

Glucose-dependent activation, activity, and deactivation of beta cell networks in acute mouse pancreas tissue slices

“…At this rate, the oscillatory behavior would reach a sustained active state (i.e., an active time of 100 %) at approx. 25 mM glucose or somewhat higher, given that the dose-response curve is probably flatter at higher concentrations (124). This is in good agreement with previous insulin secretion data, as well as [Ca 2+ ]IC imaging and electrophysiological studies (9,20,41,57,74,97).…”

High resolution analysis of the cytosolic Ca2+events in beta cell collectives in situ

“…Assessing Ca 2+ release from intracellular Ca 2+ channels requires high temporal resolution recording. To date, single-cell recording of electrophysiological parameters during glucose-dependent depolarization has been accepted as the gold standard approach to assess the function of a beta cells in islets at a millisecond time scale [15,54]. Until recently, measurements of [Ca 2+ ] c oscillations were typically orders of magnitude slower than this required temporal resolution [44].…”

Associative Conditioning Is a Robust Systemic Behavior in Unicellular Organisms: An Interspecies Comparison

“…Human pancreatic β cells have also demonstrated to exhibit associative conditioning behaviors. In short, temporal potentiation of sensitivity to glucose was achieved by replacing glucose concentrations with other secretagogues in combination with carbachol, giving rise to a newly formed behavior that could be explained by a short-term associative conditioning process ( Sanchez-Andres et al, 2020 ). Electrophysiological studies with individual Purkinje cells have showed that these organisms can remember the interval between the onset of an artificial conditioned stimulus and the onset of an artificial unconditioned stimulus ( Gallistel, 2017 ).…”