Voltage noise measurements across the pancreatic beta‐cell membrane: calcium channel characteristics.

Atwater, I; Dawson, Catherine; Eddlestone, G. T.; Rojas, Eduardo

doi:10.1113/jphysiol.1981.sp013701

Cited by 59 publications

(54 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have measured changes in [Ca 2ϩ ] i in ␤-cells pretreated with commercial TTR, which constitutes both monomeric and tetrameric forms, and stimulated with glucose and KCl, the latter to directly open the voltage-gated L-type Ca 2ϩ -channel by depolarizing the cell. The addition of 25 mM KCl will give an approximate increase in membrane potential from Ϫ60 to Ϫ30 mV (13). TTR at a concentration of 150 mg͞liter induced a more pronounced increase in [Ca 2ϩ ] i , subsequent to stimulation with glucose and KCl ( Fig.…”

Section: Resultsmentioning

confidence: 92%

Transthyretin constitutes a functional component in pancreatic β-cell stimulus-secretion coupling

Refai

Dekki

Yang

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Transthyretin (TTR) is a transport protein for thyroxine and, in association with retinol-binding protein, for retinol, mainly existing as a tetramer in vivo. We now demonstrate that TTR tetramer has a positive role in pancreatic ␤-cell stimulus-secretion coupling. TTR promoted glucose-induced increases in cytoplasmic free Ca 2؉ concentration ([Ca 2؉ ]i) and insulin release. This resulted from a direct effect on glucose-induced electrical activity and voltagegated Ca 2؉ channels. TTR also protected against ␤-cell apoptosis. The concentration of TTR tetramer was decreased, whereas that of a monomeric form was increased in sera from patients with type 1 diabetes. The monomer was without effect on glucose-induced insulin release and apoptosis. Thus, TTR tetramer constitutes a component in normal ␤-cell function. Conversion of TTR tetramer to monomer may be involved in the development of ␤-cell failure͞ destruction in type 1 diabetes.type 1 diabetes ͉ Ca 2ϩ channels ͉ insulin release ͉ ␤-cell signal transduction ͉ apoptosis T ransthyretin (TTR) is a protein that is synthesized in the liver, the choroid plexus of the brain, and the endocrine pancreas (1, 2). It is a transport protein for thyroxine and, in association with retinol-binding protein, for retinol. It has been reported that 1-2% of plasma TTR circulates bound to highdensity lipoprotein (HDL) and that the association to the HDL vesicle occurs through binding to apolipoprotein A1 (3). TTR has a complex equilibrium between different quaternary structures in serum (4),but exists mainly as a tetrameric protein of 14-kDa subunits (160-380 mg͞liter) with only a small amount of TTR monomer present in vivo in normal individuals (5, 6). Consequently, measurements of TTR in serum by conventional methods mainly reflect the tetrameric form. The TTR amyloidoses are human diseases in which misfolded TTR protein aggregates in different tissues. Several point mutations in TTR have been related to familial amyloidotic polyneuropathy (FAP) (7). The fact that TTR is also produced within the pancreatic islet made us interested in evaluating a possible role of this protein in ␤-cell stimulus-secretion coupling. MethodsIdentification of TTR in Human Sera. Sera from type 1 diabetes (T1D) patients and control subjects were collected, identically sterile-processed, heat-inactivated by incubation at 56°C for 30 min, and stored frozen at Ϫ20°C until used. Changes in cytoplasmic free Ca 2ϩ concentration ([Ca 2ϩ ] i ) were tested in ␤-cells when they were depolarized with 25 mM KCl. Those diabetic sera that induced a higher increase in [Ca 2ϩ ] i than sera from controls were centrifuged, and the supernatant was passed through a 0.45-mm sterile filter. Samples were loaded on SepPak C 18 preconditioned with 0.1% trifluoroacetic acid. After application, the sample proteins were eluted with 60% acetonitrile in 0.1% trifluoroacetic acid. This procedure was repeated twice. The two fractions were pooled, and the volume was reduced by lyophilization.The lyophilized material was submitted to...

show abstract

Section: Resultsmentioning

confidence: 92%

Transthyretin constitutes a functional component in pancreatic β-cell stimulus-secretion coupling

Refai

Dekki

Yang

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…It also induced continuous spike activity, but the amplitude ofthe spikes decreased with time. After a few minutes, there remained only small fluctuations of the membrane potential, which probably reflect Ca2" channel activity (24). Addition of 100 MM diazoxide repolarized the membrane by 7±1 mV and suppressed the small fluctuations of the membrane potential (Fig.…”

Section: Methodsmentioning

confidence: 99%

Evidence that glucose can control insulin release independently from its action on ATP-sensitive K+ channels in mouse B cells.

Gembal¹,

Gilon²,

Henquin³

1992

J. Clin. Invest.

472

386

View full text Add to dashboard Cite

Glucose stimulation of insulin release involves closure of ATPsensitive K+ channels, depolarization, and Ca2+ influx in B cells. Mouse islets were used to investigate whether glucose can still regulate insulin release when it cannot control ATP-sensitive K+ channels. Opening ofthese channels by diazoxide (100-250 Mmol/liter) blocked the effects of glucose on B cell membrane potential (intracellular microelectrodes), free cytosolic Ca2+ (fura-2 method), and insulin release, but it did not prevent those of high K (30 mmol/liter). K-induced insulin release in the presence of diazoxide was, however, dose dependently increased by glucose, which was already effective at concentrations (2-6 mmol/liter) that are subthreshold under normal conditions (low K and no diazoxide). This effect was not accompanied by detectable changes in B cell membrane potential.Measurements of 'Ca fluxes and cytosolic Ca2" indicated that glucose slightly increased Ca2+ influx during the first minutes of depolarization by K, but not in the steady state when its effect on insulin release was the largest. In conclusion, there exists a mechanism by which glucose can control insulin release independently from changes in K+-ATP channel activity, in membrane potential, and in cytosolic Ca2+. This mechanism may serve to amplify the secretory response to the triggering signal (closure of K+-ATP channels -depolarization -Ca2" influx) induced by glucose. (J. Clin. Invest. 1992. 89:1288-1295

show abstract

“…The microelectrodes had tip resistances in the range of 150-300 MS/. A detailed description of the electrophysiological methods can be found in [22].…”

Section: Methodsmentioning

confidence: 99%

Muscarinic receptor modulation of glucose‐induced electrical activity in mouse pancreatic B‐cells

Santos

Rojas

1989

FEBS Letters

View full text Add to dashboard Cite

Acetyicholine (1-10/zM) depolarized the membrane and stimulated glucose-induced bursts of electrical activity in mouse pancreatic B-cells. The acetylcholine effects were mimicked by muscarine while nicotine had no effect on membrane potential. Pirenzepine, an antagonist of the classical M l-type muscarinic receptors, but not gallamine (1-100 gM), an antagonist of the classical M2-type receptors, antagonized the acetylcholine action on glucose-induced electrical activity (ICs0 =0.25/zM). Bethanechol, an agonist of the classical M2-type musearinic receptors, was approximately 100 times less effective than acetylcholine in stimulating the electrical activity. In addition, acetylcholine (1/~M) induced a marked increase (25%) in input resistance to the B-cell membrane. The results indicate that acetylcholine exerted its effects on the B-cell membrane by inhibiting K + conductance via activation ofa musearinic receptor subtype distinct from the classical M2-type receptor.

show abstract

Voltage noise measurements across the pancreatic beta‐cell membrane: calcium channel characteristics.

Cited by 59 publications

References 31 publications

Transthyretin constitutes a functional component in pancreatic β-cell stimulus-secretion coupling

Transthyretin constitutes a functional component in pancreatic β-cell stimulus-secretion coupling

Evidence that glucose can control insulin release independently from its action on ATP-sensitive K+ channels in mouse B cells.

Muscarinic receptor modulation of glucose‐induced electrical activity in mouse pancreatic B‐cells

Contact Info

Product

Resources

About