Ca²⁺-dependent desensitization of insulin secretion by strong potassium depolarization

Abstract

Willenborg M, Belz M, Schumacher K, Paufler A, Hatlapatka K, Rustenbeck I. Ca 2ϩ -dependent desensitization of insulin secretion by strong potassium depolarization.

Gap Junction Proteins in the Blood-Brain Barrier Control Nutrient-Dependent Reactivation of Drosophila Neural Stem Cells

“…Failure to depolarize or an active block to depolarization prevents insulin release. However, sustained depolarization of β cells can lead to desensitization and a decline in insulin release (Willenborg et al., 2012). Interestingly, we find that forced depolarization of BBB glia only mildly enhances NSC reactivation (data not shown).…”

Granule Mobility, Fusion Frequency and Insulin Secretion Are Differentially Affected by Insulinotropic Stimuli

“…This may be the reason why the stimulation of secretion by both glucose and high K + was less effective than with primary islets (see, e.g. ). However, this property, although reproducible during the present investigation, is not a general property of MIN6 pseudo‐islets.…”

Insulinotropic effect of high potassium concentration beyond plasma membrane depolarization

“…Batches of 50 NMRI mouse islets were introduced in a purpose-made perifusion chamber (37°C) and perifused with a HEPES-buffered Krebs-Ringer medium (2 mg/ml BSA) saturated with 95% O 2 and 5% CO2, which contained the respective secretagogue. During phases of K ϩ depolarization, there was no reduction of the Na ϩ concentration (often done to avoid the hyperosmolarity of the incubation medium), since hyperosmolarity as such was shown to have only a modest effect on depolarizationinduced insulin secretion, whereas the reduction of the Na ϩ concentration has a complex enhancing effect (29). The insulin content in the fractionated efflux was determined by ELISA (Mercodia, Uppsala, Sweden).…”

“…phenylalkylamine D600 (methoxyverapamil), which differs from the dihydropyridine nifedipine in the binding site at L-type channels and the mode of channel block (12), was significantly effective, even though less so than CoCl 2 With respect to insulin secretion, the near inability of 15 mM K ϩ to stimulate insulin secretion in the presence of basal glucose (29) was now confirmed in direct comparison with the massive monophasic effect of 40 mM K ϩ . The most straightforward explanation is that the Ca 2ϩ increase to induce granule fusion remains subthreshold in the critical submembrane compartment (18), in spite of a clear increase of the fura fluorescence ratio.…”

“…The current consensus model would have predicted that this sequence of events should lead to a first phase-like secretion by mobilization of the limited readily releasable pool of granules (20). Instead, the immediate secretory response increased exponentially with increasing K ϩ concentration, whereas the depolarizing effect approached saturation (29).…”