Modalities of Gliclazide-induced Ca2+ Influx into the Pancreatic B-Cell

Lebrun, Philippe; Malaisse, Willy; Herchuelz, André

doi:10.2337/diacare.31.11.1010

Cited by 24 publications

(10 citation statements)

References 10 publications

(17 reference statements)

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“…In contrast to sulphonylureas (Hellman, 1981;Lebrun et al, 1982;Garrino et al, 1986), 1-adamantanamine still increased 45Ca efflux from islets perifused with a Ca-free medium. The drug thus appears to possess the additional property of mobilizing intracellular Ca2", by a mechanism that remains unknown.…”

Section: Effects Ofvarious Adamantane Derivativesmentioning

confidence: 84%

Adamantane derivatives: a new class of insulin secretagogues

Garrino¹,

Henquin

1987

British J Pharmacology

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1 Adamantane derivatives were found to increase insulin release in vitro. Mouse islets were used to study the mechanisms and molecular requirements of that hitherto unrecognised property.2 At a non-stimulatory concentration of glucose (3mM), 1-adamantanamine (1 mM) reversibly inhibited`6Rb efflux from islet cells, depolarized the P-cell membrane, induced electrical activity, stimulated 45Ca uptake and efflux, and triggered insulin release. Omission of extracellular Ca2" abolished the secretory response but only partially inhibited the acceleration of 45Ca efflux.3 At a stimulatory concentration of glucose (10 mM), 1-adamantanamine reversibly increased '8Rb efflux, potentiated electrical activity (lengthening of the slow waves with spikes), augmented 45Ca uptake and efflux, and increased insulin release. The effects of adamantanamine were dose-dependent, with a threshold concentration of 1O iM for stimulation of release. 4 2-Adamantanamine was as potent as l-adamantanamine. In contrast, substitution of the amino group by a carboxyl group (l-adamantanecarboxylic acid) decreased the effectiveness by about 65%, and substitution by a hydroxyl group (1-adamantanol) suppressed it.

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Section: Effects Ofvarious Adamantane Derivativesmentioning

confidence: 84%

Adamantane derivatives: a new class of insulin secretagogues

Garrino¹,

Henquin

1987

British J Pharmacology

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“…The stimulatory effect of hypoglycemic sulfonylureas on the secretory process is totally abolished in Ca 2+ -deprived medium, whereas verapamil, a Ca 2 + -entry blocker, provokes a dose-dependent inhibition of gliclazide-induced insulin output (67,68). The stimulatory effect of hypoglycemic sulfonylureas on the secretory process is totally abolished in Ca 2+ -deprived medium, whereas verapamil, a Ca 2 + -entry blocker, provokes a dose-dependent inhibition of gliclazide-induced insulin output (67,68).…”

Section: Ca 2 + Inflowmentioning

confidence: 99%

Mechanisms of Sulfonylurea-lnduced Insulin Release

Malaisse¹,

Lebrun²

1990

Diabetes Care

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The mechanisms responsible for the stimulation of insulin release from the pancreatic beta-cell by hypoglycemic sulfonylureas are reviewed herein. One hypothesis postulates that these agents act, at the level of the plasma membrane, by causing the closure of a class of K+ channels characterized by their sensitivity to ATP. This may lead to depolarization of the plasma membrane, gating of voltage-sensitive Ca2+ channels, increase in cytosolic Ca2+ activity, and activation of the effector system for insulin release. However, it is not evident that the closure of ATP-sensitive K+ channels accounts for effects of sulfonylureas such as inhibition of K+ inflow into the islet cells, increase in their Na+ content, or even stimulation of Ca2+ inflow and insulin release at physiological or higher concentrations of D-glucose.

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“…However, have reported that tolbutamide induced a transient rise in 86Rb+ efflux but had no effect on the steady-state efflux. It has also been found that sulphonylureas transiently stimulate 45Ca2+ influx and efflux (Henquin, 1980;Malaisse et al 1980;Lebrun et al 1982). However, this could be associated with induced spike activity.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological Evidence for the Inhibition of Potassium Permeability in Pancreatic Β‐cells by Glibenclamide

et al. 1984

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SUMMARYThe effects of glibenclamide on the electrical activity of the fl-cells of the islets of Langerhans of normal mice have been investigated in the absence and presence of glucose (11 1 mM). Glibenclamide depolarized the cell membrane and this has been interpreted in terms of an increase in the ratio of the Na+ and K+ permeabilities, PNa/PK. This ratio increased from 0 05 to 0 24 in the presence of 4 /tM glibenclamide and zero glucose. The input resistance of the fl-cells also increased. These observations indicate a decrease in K+ permeability. The effect is only slowly reversed after removal of glibenclamide. Uncouplers of oxidative phosphorylation do not reverse the depolarization induced by glibenclamide. It is suggested that glibenclamide is acting directly to inhibit the [Ca2+]i-gated K+ permeability in the fl-cell membrane.

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Modalities of Gliclazide-induced Ca2+ Influx into the Pancreatic B-Cell

Cited by 24 publications

References 10 publications

Adamantane derivatives: a new class of insulin secretagogues

Adamantane derivatives: a new class of insulin secretagogues

Mechanisms of Sulfonylurea-lnduced Insulin Release

Electrophysiological Evidence for the Inhibition of Potassium Permeability in Pancreatic Β‐cells by Glibenclamide

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