Effects of octane derivatives on activity of the volume-regulated anion channel in rat pancreatic β-cells

Abstract

Abstract:Background: Saturated free fatty acids (FFAs) have a dual action on pancreatic b-cells, consisting of an initial enhancement and subsequent suppression of glucose-induced electrical activity and insulin release. These stimulatory and inhibitory effects have been attributed, at least in part, to the activation and inhibition, respectively, of the volume-regulated anion channel (VRAC) by FFAs. Both effects were independent of their metabolism. We have now investigated the effects of related aliphatic compounds in order to further define the determinants of FFA interaction with VRAC. Methods: b-Cell VRAC and electrical activity were measured by conventional whole-cell and perforated patch recording, respectively. Cell volume was measured using a video-imaging technique. Results: In common with octanoic acid, addition of methyl octanoate or n-octanol resulted in a rapid, pronounced and reversible inhibition of VRAC activity. Addition of n-octane had no significant effect on VRAC activity. n-Octanol had a biphasic effect on b-cell membrane potential, namely a small transient depolarization followed by a marked hyperpolarization. n-Octanol was also found to prevent regulatory volume decrease in cells exposed to a hypotonic medium, consistent with VRAC inhibition. Conclusion: It is suggested that methyl octanoate and n-octanol can mimic the effects of FFAs on the pancreatic b-cell via modulation of VRAC activity. The structural requirements for this effect appear to be a medium or long chain aliphatic compound containing at least one oxygen atom.

Mechanisms of octanoic acid potentiation of insulin secretion in isolated islets

“…Two distinct IP3 receptor inhibitors either diminished the OA-induced increase in [Ca 2+ ] i in insulinoma MIN6 cells 35 or abolished the OA-induced increase in [Ca 2+ ] i in Sur1 -/mouse islets (this study). Studies by Best et al showed that OA caused a transient potentiation of glucose-induced electrical activity and a transient increase in VSAC activity in rat βcells, 32 also consistent with our observations. However, the electrophysiologic studies by Best et al showed that after the initial activation of VSACs, OA caused a gradual hyperpolarization and a prolonged inhibition of electrical activity, 32 a phenomenon which we did not observe in our mouse islet measurements.…”

“…Studies by Best et al showed that OA caused a transient potentiation of glucose-induced electrical activity and a transient increase in VSAC activity in rat βcells, 32 also consistent with our observations. However, the electrophysiologic studies by Best et al showed that after the initial activation of VSACs, OA caused a gradual hyperpolarization and a prolonged inhibition of electrical activity, 32 a phenomenon which we did not observe in our mouse islet measurements. Nevertheless, our results generally support the concept that OA may play its potentiating effect on insulin secretion via VSACs.…”

“…We speculated that VSACs might be involved in the potentiation effect of OA on insulin secretion because previous reports have suggested that OA modulates VSACs, which are known to play a role in GSIS. [28][29][30][31][32] Figure 5(a) shows that Sur1 -/islets have elevated basal [Ca 2+ ] i , which is further increased by 1 mM OA, in contrast to the lack of response to OA in WT islets. This contrasting observation is consistent with the insulin secretion results shown in Figure 3.…”

Impact of Feeding Probiotics on Blood Parameters, Tail Fat Metabolites, and Volatile Flavor Components of Sunit Sheep

“…It is added to some foods as a food flavor and is also used as a raw material for the production of caprylaldehyde and caprylic acid [ 38 , 39 ]. Some studies have shown that octanol has a two-way regulatory effect on the membrane potential of rat pancreatic β-cells and enhances the activity of volume-regulated anion channels [ 40 ]. Caprylic acid is a monocarboxylate saturated fatty acid involved in ketogenic metabolism.…”