Nutrient insulin secretagogues decrease 45Ca2+ efflux from islet cells by a mechanism other than the inhibition of the Na+‐Ca2+ countertransport

Henquin, Jean‐Claude; Miguel, Rosario de; Garrino, Maria-Grazia; Hermans, Mp.; Nenquin, Myriam

doi:10.1016/0014-5793(85)81237-0

Cited by 12 publications

(4 citation statements)

References 21 publications

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“…Although the insulin-secretory response to glucose of islets from ob/ob mice has the same general characteristics as that of islets from lean mice, the regulation of the response is clearly aberrant in electrophysiological (Rosario et al, 1985;Rosario, 1985) and in biochemical terms. Our data therefore support the suggestion (Henquin et al, 1985) that insulin secretion in the ob/ob mouse does not follow the normal process, but rather is an important part of the pathology characteristic of this animal model.…”

Section: Discussionsupporting

confidence: 89%

Abnormal regulation of insulin secretion in the genetically obese (ob/ob) mouse

Black¹,

Heick²,

Bégin–Heick³

1986

Biochemical Journal

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To determine whether the abnormal insulin-secretory activity encountered in obese mice is due to an anomaly in the production of cyclic AMP, islets of lean and obese mice were incubated with forskolin under various conditions. Our data show that, in addition to the well-known quantitative differences in insulin-secretory activity between islets of lean and obese mice, there are important qualitative differences. The islets of obese mice accumulated less cyclic AMP than did those of lean mice in response to given doses of forskolin, yet their insulin secretion was enhanced to much higher values. In the islets of obese mice, but not in those of lean mice, the stimulatory effect of forskolin on insulin secretion was evident even at non-stimulatory concentrations of glucose or in Ca2+-deprived incubation media, showing that the islet of the obese mouse is less dependent on a primary stimulus (glucose) and on the provision of normal concentrations of Ca2+ in the bathing medium than is the islet of the lean mouse.

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Section: Discussionsupporting

confidence: 89%

Abnormal regulation of insulin secretion in the genetically obese (ob/ob) mouse

Black¹,

Heick²,

Bégin–Heick³

1986

Biochemical Journal

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“…This paradoxical inhibitory effect of a low concentration of glucose is reminiscent of the reports that glucose also prevents the mobilization of cellular Ca2+ by alanine (Charles & Henquin, 1983), and inhibits insulin release induced by Na+ mobilization of intracellular Ca2+ (Hellman, Honkanen & Gylfe, 1982). These data are compatible with the hypothesis that glucose favours Ca2+ sequestration in f-cell organelles or, at least, decreases the ability of Na+ to mobilize it (Hellman & Gylfe, 1984;Henquin, de Miguel, Garrino, Hermans & Nenquin, 1985).…”

Section: Effects Of Alaninesupporting

confidence: 81%

Cyclic adenosine monophosphate differently affects the response of mouse pancreatic beta‐cells to various amino acids.

Henquin¹,

Meissner²

1986

The Journal of Physiology

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SUMMARY1. The membrane potential of mouse ,8-cells was measured in parallel with 86Rb+ efflux and insulin release from mouse islets during stimulation by three types of amino acids and modulation of their effects by glucose and cyclic adenosine monophosphate (cyclic AMP) (forskolin being used to activate the adenylate cyclase).2. In the absence of glucose, alanine and arginine accelerated 86Rb+ efflux, whereas leucine decreased it. They all depolarized the fl-cell membrane and slightly increased insulin release. Forskolin had little effect on 86Rb+ efflux, consistently potentiated insulin release but induced electrical activity only in the presence of leucine.3. The effects of the three amino acids on 86Rb+ efflux and fl-cell membrane potential were not qualitatively altered by a non-stimulatory concentration of glucose (3 mM). However, the release of insulin induced by leucine alone or with forskolin was markedly amplified, in contrast to that of alanine or arginine, which was inhibited.4. In the presence of a threshold concentration of glucose (7 mM), the three amino acids accelerated s6Rb+ efflux and depolarized the fl-cell membrane. With alanine and arginine, spike activity was transiently observed and coincided with a short-lived increase in insulin release. With leucine, slow waves with superimposed bursts of spikes occurred and were accompanied by a sustained release of insulin. Forskolin alone also triggered slow waves and bursts of spikes, and increased insulin release. Both effects were larger in the presence of arginine, but not in the presence of alanine. Forskolin considerably increased the electrical and secretary effects of leucine.5. A higher concentration of glucose (10 mM) induced slow waves with bursts of spikes in all cells and stimulated insulin release. Alanine, arginine and leucine increased 86Rb+ efflux, electrical activity and insulin release. However, the changes produced by the three amino acids displayed different time course, amplitude and characteristics. Forskolin potentiated insulin release and electrical activity induced by glucose alone. These effects were not augmented by alanine, but markedly amplified by arginine or leucine.6. Several conclusions can be drawn from this study.

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“…Extracellular Na + is also required for normal insulin secretion from both human and rodent islets [25–30]. Rodent β‐cell APs fire in the absence of extracellular Ca 2+ during glucose‐induced depolarization; however, when Na + is also removed with Ca 2+ the APs fail to fire, implicating an important role for Na + influx during the AP [30,31].…”

Section: Initiation Of the Ap: Katp Ca2+ And Na+ Channelsmentioning

confidence: 99%

Action potentials and insulin secretion: new insights into the role of Kv channels

Jacobson

Philipson

2007

Diabetes Obesity Metabolism

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Coordinated electrical activity allows pancreatic b-cells to respond to secretagogues with calcium entry followed by insulin secretion. Metabolism of glucose affects multiple membrane proteins including ion channels, transporters and pumps that collaborate in a cascade of electrical activity resulting in insulin release. Glucose induces b-cell depolarization resulting in the firing of action potentials (APs), which are the primary electrical signal of the b-cell. They are shaped by orchestrated activation of ion channels. Here we give an overview of the voltage-gated potassium (Kv) channels of the b-cell, which are responsible in part for the falling phase of the AP, and how their regulation affects insulin secretion. b cells contain several Kv channels allowing dynamic integration of multiple signals on repolarization of glucose-stimulated APs. Recent studies on Kv channel regulation by cAMP and arachidonic acid and on the Kv2.1 null mouse have greatly increased our understanding of b-cell excitation-secretion coupling.

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Nutrient insulin secretagogues decrease ⁴⁵Ca²⁺ efflux from islet cells by a mechanism other than the inhibition of the Na⁺‐Ca²⁺ countertransport

Cited by 12 publications

References 21 publications

Abnormal regulation of insulin secretion in the genetically obese (ob/ob) mouse

Abnormal regulation of insulin secretion in the genetically obese (ob/ob) mouse

Cyclic adenosine monophosphate differently affects the response of mouse pancreatic beta‐cells to various amino acids.

Action potentials and insulin secretion: new insights into the role of Kv channels

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