Dual effects of glucose on the cytosolic Ca²⁺ activity of mouse pancreatic β‐cells

Abstract

The cytosolic Ca2+ activity of mouse pancreatic &cells was studied with the intracellular fluorescent indicator quin2. When the extracellular Ca2+ concentration was 1.20 mM, the basal cytosolic Ca2+ activity was 162 + 9 nM. Stimulation with 20 mM glucose increased this Ca2+ activity by 40%. In the presence of only 0.20 mM Ca2+ or after the addition of the voltage-dependent Ca2+ -channel blocker D-600, glucose had an opposite and more prompt effect in reducing cytosolic Ca2' by about 15%. It is concluded that an early result of glucose exposure is a lowering of the cytosolic Ca2+ activity and that this effect tends to be masked by a subsequent increase of the Ca2+ activity due to influx of Ca2+ through the voltagedependent Ca2+ channels. Cytosolic Ca2' Quin2Insulin secretion

Glucose-induced accumulation of inositol trisphosphates in isolated pancreatic islets. Predominance of the 1,3,4-isomer

“…Moreover, the progressive glucose-induced accumulation of Ins(1,3,4)P3 in the presence of Li+ seems to imply that the rate of Ins(1,4,5)P3 generation remains higher in islets incubated with 28 mM-glucose than in islets with 3 mM-glucose for at least 5 min. This assumes that Ins(1,3,4)P3 is generated via the sequential actions of an Ins(1,4,5)P3 3-kinase and of an Ins(1,3,4,5)P3 5-phosphomonoesterase, as seems likely (Batty et al, 1985;Michell, 1986).Ins(1,4,5)P3 may therefore participate in the increase in islet intracellular Ca2+ believed to occur on glucose stimulation (Rorsman et al, 1984), possibly in concert with other Ca2+-mobilizing substances, including arachidonic acid (Wolf et al, 1986).…”

“…Exogenous Ins (1,4,5)P3 at concentrations between 1 and 10 /uM induces release of 45Ca2+ from the endoplasmic reticulum of digitoninpermeabilized islets and of insulinoma cell lines Joseph et al, 1984;Prentki et al, 1984), and insulin secretion is stimulated in permeabilized islets by increasing the ambient free Ca2+ concentration within the submicromolar range (Colca et al, 1985). At concentrations that stimulate insulin secretion, glucose appears to increase the cytosolic Ca2+ concentration in intact islet cells (Rorsman et al, 1984;Wollheim & Sharp, 1981) and to induce the release from [3H]inositol-labelled islets of material with the properties of an inositol trisphosphate on chromatography over Dowex AG1-X8 ion-exchange resin (Best & Malaisse, 1984;Montague et al, 1985;Morgan et al, 1985).…”

Increase in insulin release from rat pancreatic islets by quinolone antibiotics

“…Since LFLX shifted the dose-response curve of glucose-induced insulin release to the left without affecting the maximal release, the quinolone was considered to act through mechanisms also involved in glucose-induced insulin release. The sugar is known to activate three major second messenger systems (Malaisse-Lagae & Malaisse, 1971;Fex & Lernmark, 1972;Charles et al, 1973;Tanigawa et al, 1982;Rorsman et al, 1984;Prentki & Matschinsky, 1987 (Sugden & Ashcroft, 1981;Lipson & Oldham, 1983), which will be caused by LFLX.…”

Calcium and delayed potassium currents in mouse pancreatic beta‐cells under voltage‐clamp conditions.

“…Glucose-induced insulin release from pancreatic fl-cells is known to involve an increased Ca2+ activity of the cytoplasm (Prentki & Wollheim, 1984;Rorsman, Abrahamsson, Gylfe & Hellman, 1984). It is believed that this increment mainly results from a stimulated influx of extracellular Ca2+ through voltage-dependent Ca2+ channels (Dean & Matthews, 1970).…”