Ionic Effects on the Uptake of Sulfonylurea (Glibenclamide) by Pancreatic Islets

Hellman, Bo; Sehlin, Janove; Ib, Täljedal

doi:10.1055/s-0028-1093606

Cited by 10 publications

(3 citation statements)

References 2 publications

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“…The only puzzling thing is that glucose and acetylcholine acted in opposite directions. Perhaps this paradox has something to do with the fact that the fluorescent signal responds to changes in the concentration of calcium as well as Mg2+ [51]. That sulfonylureas influence ionic fluxes in the islets has also been demonstrated [52][53][54].…”

Section: Fluorescent Probing Of Calcium In Islet Cellsmentioning

confidence: 99%

On insulin secretion

Täljedal

1981

Diabetologia

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Aspects of insulin secretory mechanisms and models of diabetogenic B cell damage are discussed. Measurements of fluxes of 3H-labelled triphenylmethylphosphonium ion, 86Rb+, 42K+, 22Na+, and 45Ca2+ in isolated islets indicate that the triggering of insulin release depends on alterations in the interaction of ions with the B cells. One difficulty in the detailed analysis of these alterations are uncertainties which arise when macroscopic concepts for homogenous phases are applied to microscopic and heterogenous compartments, as exemplified by the meaning of pH in insulin secretory granules and of membrane electric potential. Nonetheless, the importance of an apparent decreased K+ permeability in mediating the insulin-releasing action of glucose, and of an apparent increased Na+ permeability in mediating the potentiating action of acetylcholine is emphasized. Fluorescent probing of Ca2+ by chlorotetracycline revealed effects of glucose alone as well as glucose-dependent and atropine-sensitive effects of acetylcholine. Although acetylcholine, sulfonylureas, and certain thiol-blocking agents may stimulate insulin release by direct effects on the B cell plasma membrane, a high capacity for D-glucose transmembrane transport has probably evolved in order that the interior of the B cells can always sense the circulating glucose concentration. A signal to secretion is thought to be transmitted from glucose metabolism to altered ion fluxes by intervention of reduced pyridine nucleotides and hypothetical redox protein for which thioredoxin may be a model. The insulin secretory defect in hereditary diabetic C57BL/KsJ-db/db-mice is apparently linked to a decreased basal permeability for K+ and a failure of the B cells to decrease further this permeability in response to glucose. Functioning B cells are acutely damaged when exposed to heterologous serum or alloxan in vitro; cytotoxic activation of complement by the alternative pathway could perhaps occur during islet inflammation. Protection experiments with free-radical scavengers in vitro and in vivo support the theory that hydroxyl radicals are instrumental in the production of alloxan diabetes. Rapid reduction of alloxan by thioredoxin in the presence of molecular oxygen and NADPH leads to strong chemiluminescence from luminol indicative of an intense radical protection. The sensitivity of B cells to alloxan may be due to physiological specializations of their plasma membranes, involving the highly effective glucose carrier or the hypothetical oxidation/reduction systems or both.

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Section: Fluorescent Probing Of Calcium In Islet Cellsmentioning

confidence: 99%

On insulin secretion

Täljedal

1981

Diabetologia

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“…There is little doubt that ionic mechanisms are important both for the sulphonylurea binding to the ß-cells (Hellman et al 1976b) and for the subsequent stimulation of their secretory activity (Henquin 1980). The key role of Ca2+ in the sulphonylurea stimulation of insulin release is apparent both from the need of this ion in the extracellular medium (Curry et al 1968) as well as from the observations of altered transmembrane 45Ca fluxes seen when isolated islets are exposed to sulphonylureas (Hellman et al 1977;Kavazu et al 1980;Henquin 1980;Hellman 1981).…”

mentioning

confidence: 95%

Glibenclamide is exceptional among hypoglycaemic sulphonylureas in accumulating progressively in β-cell-rich pancreatic islets

Hellman

Sehlin

Täljedal

1984

Acta Endocrinologica

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“…According to Hellman and his colleagues, hypoglycaemic sulphonylureas do not penetrate the pancreatic #-cell beyond its plasma membrane (Hellman, Sehlin & Taljedal, 1971;1973b;1976;Hellman, Lernmark, Sehlin & Taljedal, 1973a;Hellman & Taljedal, 1975). This finding suggests that the primary site of action of these drugs may be located at the level of *the cell boundary, as defined elsewhere (Orci, Ravaz-zola, Amherdt & Malaisse-Lagae, 1974).…”

Section: Introduction Methodsmentioning

confidence: 96%

Synergistic Effects of Hypoglycaemic Sulphonylureas and Antibiotic Ionophores Upon Calcium Translocation

Couturier¹,

Malaisse²

1980

British J Pharmacology

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1 Hypoglycaemic sulphonylureas, such as tolbutamide and gliclazide, provoke the translocation of calcium from an aqueous medium into or across a hydrophobic region. The combined effect of sulphonylureas and antibiotic ionophores upon such a process was investigated. 2 The magnitude of the sulphonylurea-induced translocation of calcium was more marked in the presence than in the absence of A23187. Gliclazide and tolbutamide also enhanced, although less markedly, X537A-mediated calcium translocation. The effect of the sulphonylureas was even less marked in the presence of both ionophores, which acted synergistically in causing calcium translocation.3 A non-hypoglycaemic sulphonylurea and diazoxide failed to affect ionophore-mediated calcium translocation. Gliclazide failed to enhance X537A-mediated sodium translocation. 4 It is proposed that the primary site of action of hypoglycaemic sulphonylureas upon calciumdependent physiological processes may correspond to a drug-induced facilitation of calcium transport across the plasma membrane, as mediated by native ionophores. IntroductionMethods

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Ionic Effects on the Uptake of Sulfonylurea (Glibenclamide) by Pancreatic Islets

Cited by 10 publications

References 2 publications

On insulin secretion

On insulin secretion

Glibenclamide is exceptional among hypoglycaemic sulphonylureas in accumulating progressively in β-cell-rich pancreatic islets

Synergistic Effects of Hypoglycaemic Sulphonylureas and Antibiotic Ionophores Upon Calcium Translocation

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