Differential effects of the K<sup>+</sup> channel blockers apamin and quinine on glucose‐induced electrical activity in pancreatic β‐cells from a strain of ob/ob (obese) mice

Rosário, Luı́s M.

doi:10.1016/0014-5793(85)80391-4

Cited by 12 publications

(5 citation statements)

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“…Among other features, this electrical pattern is characterized by a higher sensitivity to low glucose concentrations. This hyper-excitability has been related to altered K + permeabilities (Fournier et al, 1990;Rosario, 1985). These observations would be in accordance with the lower density of KATP channels in the membrane of β-cells from ob/ob mice (Park et al, 2013).…”

Section: Discussionsupporting

confidence: 68%

See 1 more Smart Citation

Enhanced glucose-induced intracellular signaling promotes insulin hypersecretion: Pancreatic beta-cell functional adaptations in a model of genetic obesity and prediabetes

Irles

Ñeco

Lluesma

et al. 2015

Molecular and Cellular Endocrinology

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Section: Discussionsupporting

confidence: 68%

“…Statistical significance is indicated: ***p ≤ 0.001. Rosario, 1985;Rosario et al, 1985). It has been reported that higher action potentials may be associated to increased inward Ca 2+ currents due to the voltage-dependence characteristics of Ca 2+ channels (Gonzalez et al, 2013;Houamed et al, 2010;Jacobson et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Enhanced glucose-induced intracellular signaling promotes insulin hypersecretion: Pancreatic beta-cell functional adaptations in a model of genetic obesity and prediabetes

Irles

Ñeco

Lluesma

et al. 2015

Molecular and Cellular Endocrinology

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“…The apparent lack of effect of 4-AP on the voltage-sensitive K+ permeability of/3-cells (at concentrations that did not reduce the glucose metabolism) is not unique. In this sense, apamin, a Ca2+-dependent K+ permeability blocker, also failed to effect this permeability in /-cells from normal rats and mouse (Lebrun, Atwater, Claret, Malaisse & Herchuelz, 1983;Rosa'rio, 1985) but not from obese mice (Rosario, 1985). Finally, the present observation also agrees with the findings of , where a delayed outward K+ current induced in single mouse ,-cells was completely blocked by 20 mm TEA but only partialy blocked by 5mM 4-AP.…”

Section: Discussionsupporting

confidence: 91%

CATION TRANSPORT BY PANCREATIC β‐CELLS: EFFECT OF 4‐AMINOPYRIDINE ON ⁸⁶Rb⁺ AND ⁴⁵Ca²⁺ FLUXES

et al. 1987

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SUMMARYThe effects of 4-aminopyridine (4-AP) on insulin release, glucose oxidation and 86Rb+ and 45Ca2+ fluxes of rat isolated islets were studied. 4-AP (0 1 and 10 mM) did not alter the 86Rb+ fractional efflux. However, 10 mm 4-AP significantly increased the 86Rb+ fractional efflux. 10 mM 4-AP also reduced the insulin release from islets incubated over 90 min in the presence of both 6 and 16-7 mm glucose and from perifused islet in the presence of 16-7 mm glucose. 4-AP (10 mM) only transiently increased the insulin release and the 45Ca2+ fractional efflux in the presence of 6 mm glucose. The 45Ca2+ fractional efflux was not changed when the islets were perifused at higher glucose concentration. At zero, 6 or 16-7 mm glucose, 4-AP (10 mM) significantly increased the 45Ca2+ net uptake by islets incubated for 90 min. 10 mm 4-AP significantly reduced the glucose oxidation of islets incubated for 120 min in the presence of 16 7 mm glucose. The effects of 10 mm 4-AP on the dynamics of insulin release and 86Rb+ fractional efflux were poorly reversible. In conclusion, 4-AP, at concentrations that did not alter the glucose metabolism, (0-1 and 1 mM), failed to affect the K+ permeability in fl-cells as judged by the measurements of 86Rb+ fractional efflux. At higher concentrations (10 mM) 4-AP increased 86Rb+ efflux, decreased glucose metabolism and reduced insulin release.

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“…Elec trophysiological tests have shown that integrity of ion channels may be impaired in pancreatic islets of obob mice (161). Islets from obese mice were characterized by a more depolarized membrane than were those in lean mice (160). Quinine, which blocks the ATP-sensitive K + -activated ion channel, and apamin, which blocks the Ca 2+ -activated K + channel, have atypical effects on islets from obese mice.…”

Section: Ratsmentioning

confidence: 99%

Animal Models of Obesity: Genetic Aspects

Johnson¹,

Greenwood²,

Horwitz

et al. 1991

Annu. Rev. Nutr.

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Among the candidate genes that have been reviewed herein, adipsin, calcitonin, cholecystokin, Gi alpha and Gs subunits of G proteins, insulin I and II, and lipoprotein lipase have all been mapped to specific chromosomes in mouse or rat or both. In none of these cases is the chromosomal location syntenic with murine obesity genes db (on chromosome 4), or ob (on chromosome 6). Thus, all of these genes that code for metabolic modulators that are altered in obese animals but not in lean animals can be ruled out as possible loci of the primary genetic defect, at least for the murine models of obesity. In the case of neuropeptide Y, growth hormone, glucose transporter GLUT-4, the insulin receptor, and glyceraldehyde-3-phosphate dehydrogenase, chromosomal mapping has not yet been reported. However, in each of these cases, the evidence available strongly argues against any one of these physiologic modulators as the likely site of the primary defect for any one of the obesity mutations. Rather, in all of these cases, regardless of whether or not the gene has been mapped, the evidence suggests that posttranscriptional and/or post-translational processes are involved in bringing about the specific alterations in level or activity of the protein product that is seen in the obese animal. Often hormonal regulation is invoked as a possible explanation for the changes observed in gene expression. The hormones most commonly identified as having a mediating effect on the particular metabolic pathways involved are insulin and/or the adrenal glucocorticoids. Since in each of the obese mutants, circulating amounts of these hormones are elevated, severely so in the case of insulin, it would not be surprising to find that they influence the levels and activities of many protein products involved in a variety of central nervous system and peripheral metabolic pathways. Glucocorticoids are known to exert direct effects on gene expression; however, with respect to adipsin gene expression, a direct effect has not been found. Furthermore, insulin itself has been considered as a candidate for the genetic lesion in these animals and has been ruled out by chromosomal localization. Thus, while it may certainly prove to be the case that both insulin and glucocorticoids affect these systems in some way, their effects appear to be indirect. The work by Platt and colleagues in transgenic mice provides the first evidence of signal transduction between an obese mutant allele and the promoter sequence for a gene that shows significantly altered expression in the obese animal.(ABSTRACT TRUNCATED AT 400 WORDS)

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Differential effects of the K⁺ channel blockers apamin and quinine on glucose‐induced electrical activity in pancreatic β‐cells from a strain of ob/ob (obese) mice

Cited by 12 publications

References 14 publications

Enhanced glucose-induced intracellular signaling promotes insulin hypersecretion: Pancreatic beta-cell functional adaptations in a model of genetic obesity and prediabetes

Enhanced glucose-induced intracellular signaling promotes insulin hypersecretion: Pancreatic beta-cell functional adaptations in a model of genetic obesity and prediabetes

CATION TRANSPORT BY PANCREATIC β‐CELLS: EFFECT OF 4‐AMINOPYRIDINE ON ⁸⁶Rb⁺ AND ⁴⁵Ca²⁺ FLUXES

Animal Models of Obesity: Genetic Aspects

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Differential effects of the K+ channel blockers apamin and quinine on glucose‐induced electrical activity in pancreatic β‐cells from a strain of ob/ob (obese) mice

Cited by 12 publications

References 14 publications

Enhanced glucose-induced intracellular signaling promotes insulin hypersecretion: Pancreatic beta-cell functional adaptations in a model of genetic obesity and prediabetes

Enhanced glucose-induced intracellular signaling promotes insulin hypersecretion: Pancreatic beta-cell functional adaptations in a model of genetic obesity and prediabetes

CATION TRANSPORT BY PANCREATIC β‐CELLS: EFFECT OF 4‐AMINOPYRIDINE ON 86Rb+ AND 45Ca2+ FLUXES

Animal Models of Obesity: Genetic Aspects

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Differential effects of the K⁺ channel blockers apamin and quinine on glucose‐induced electrical activity in pancreatic β‐cells from a strain of ob/ob (obese) mice

CATION TRANSPORT BY PANCREATIC β‐CELLS: EFFECT OF 4‐AMINOPYRIDINE ON ⁸⁶Rb⁺ AND ⁴⁵Ca²⁺ FLUXES