Protein kinase C isoform specificity of cholinergic potentiation of glucose-induced pulsatile 5-HT/ insulin release from mouse pancreatic islets

Baldeiras, Inês; Santos, Rosa M.; Rosário, Luı́s M.

doi:10.4067/s0716-97602006000300014

Cited by 5 publications

(4 citation statements)

References 36 publications

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“…Findings showed that serotonin loaded into the beta cells localizes to the insulin secretory granules and is additionally co-released with it [26,27]. These authors demonstrated that there is little exocytotic activity of insulin + 5-HT at the basal glucose level, but increasing the sugar concentration results in increased insulin release from perfused beta cells.…”

Section: Peripheral Mechanismsmentioning

confidence: 74%

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Effect of Tianeptine on Glucose Tolerance with Insulin Secretion in Human: Potential Anti-Diabetic Effect of the Drug

Lechín¹,

Dijs²,

Maldonado³

et al. 2009

TONEUROEJ

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Due to the fact that drugs which interfere with the serotonin (5-HT) uptake (doxepin, sertraline, fluvoxamine and fluoxetine), were able to minimize the insulin release from islet beta-cells and counteract hypoglycemia, we investigated the effects of tianeptine, a drug which enhances 5-HT uptake during the oral glucose tolerance test. We found that the drug triggered significant and sustained insulin rises which were opposite to the plasma glucose decreases. The fact that significant noradrenaline/adrenaline (NA/Ad) plasma ratio paralleled insulin rises throughout the test is consistent with the excitatory role played by the peripheral neural sympathetic activity. Additionally, the positive correlations registered between NA versus DA (dopamine) plasma levels indicate that the latter arose from sympathetic nerves rather than the adrenal glands. Furthermore, the significant reductions of both platelet and plasma 5-HT registered throughout the OGTT plus tianeptine test support the postulation that reduction of the parasympathetic drives is occurring. This parasympathetic drive is responsible for the secretion of 5-HT from the enterochromaffin cells. Finally, considering that circulating 5-HT excites alpha-cells and modulates beta-cells, it is possible to infer that minimization of this factor contributed to the insulinogenic effect displayed by the association of this drug to an oral glucose load. We also discussed the peripheral and central nervous system mechanisms responsible for the insulinogenic effect registered throughout the test.

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Section: Peripheral Mechanismsmentioning

confidence: 74%

“…It is incorporated into the insulin granules of the former [22,23], at which level exerts a modulatory effect [24][25][26][27]. Conversely, 5-HT facilitates the secretion of glucagon from the alpha cells into the blood stream [21,[28][29][30].…”

Section: Peripheral Mechanismsmentioning

confidence: 99%

Effect of Tianeptine on Glucose Tolerance with Insulin Secretion in Human: Potential Anti-Diabetic Effect of the Drug

Lechín¹,

Dijs²,

Maldonado³

et al. 2009

TONEUROEJ

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“…Raising the [Ca 2+ ] o from 2.56 to 12.8 mM evoked a pattern of oscillatory 5-HT release (leftmost portion of the trace in Fig. 5C) resembling that evoked by glucose under standard conditions [30]. Importantly, raising glucose concentration stepwise in the range 3-30 mM caused successive increments in the amount of 5-HT released per oscillation at the steady-state, as evidenced by an increase in both amplitude and duration of the individual oscillations (trace in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Release of pre-loaded 5-HT was monitored amperometrically using beveled glass-encased carbon fiber microelectrodes implanted in a single islet, as described [8,30]. Briefly, amperometric currents were measured using a pico-amperometer with the working electrode held at +0.55 V vs. Ag/AgCl.…”

Section: -Ht Releasementioning

confidence: 99%

Regulation by Glucose of Oscillatory Electrical Activity and 5-HT/Insulin Release from Single Mouse Pancreatic Islets in Absence of Functional KATP Channels

et al. 2008

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Abstract. The glucose sensitivity of bursting electrical activity and pulsatile insulin release from pancreatic islets was determined in absence of functional K ATP channels. Membrane potential, [Ca 2+ ] i and 5-HT/insulin release were measured by intracellular recording, fura-2 fluorescence and 5-HT amperometry, respectively. Single mouse islets, bathed in tolbutamide or glibenclamide and high extracellular Ca 2+ (Ca 2+ o ), displayed bursting activity and concomitant fast [Ca 2+ ] i and 5-HT/insulin oscillations. Sulphonylurea block of K ATP channel current was unaffected by raising Ca 2+ o . Raising glucose or α-ketoisocaproic acid (KIC) concentration from 3 to 30 mM increased spiking activity and burst plateau duration. Staurosporine did not impair glucose potentiation of electrical activity, ruling out the involvement of serine/ threonine kinases. Glucose enhanced both [Ca 2+ ] i and 5-HT/insulin oscillatory activity, causing a ~3-fold increase in overall 5-HT release rate. Cells lacking bursting activity in high Ca 2+ o and low glucose (or KIC) developed a pattern of intensified spiking in response to 11 mM glucose. It is concluded that β-cells exhibit graded oscillatory electrical and secretory responses to glucose in absence of functional K ATP channels. This suggests that, under physiological conditions, early glucose sensing may involve other channels besides the K ATP channel. PANCREATIC β-cells secrete insulin in response to glucose and, thus, play a pivotal role in glucose homeostasis. The initial triggering events are relatively well understood. The ATP-sensitive K + (K ATP ) channel, in particular, represents a crucial link between glucose metabolism and Ca 2+ entry. Increasing glucose concentration raises the cytosolic ATP/ADP ratio, closing K ATP channels and evoking the depolarization required to initiate electrical activity [1]. Employing intracellular Ca 2+ clamping techniques, an amplifying pathway (also known as K ATP channel-independent pathway) for Ca 2+ -dependent insulin release has been uncovered [2, 3] whose mediators remain elusive [4,5]. β-Cells undergo cyclic changes in membrane potential, with Ca 2+ -dependent action potentials superimposed on the depolarized plateaus, the duration of which increases as glucose concentration is raised above threshold (~6-7 mM). Bursting electrical activity is matched by prominent fast oscillations of cytosolic free Ca 2+ concentration ([Ca 2+ ] i ) and insulin release (or insulin tracers such as 5-HT), measured at the single islet level [6][7][8]. Bursting electrical activity has also been recorded in vivo [9], suggesting that oscilla-

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Protein kinase C

2009

Class 2 Transferases

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Protein kinase C isoform specificity of cholinergic potentiation of glucose-induced pulsatile 5-HT/ insulin release from mouse pancreatic islets

Cited by 5 publications

References 36 publications

Effect of Tianeptine on Glucose Tolerance with Insulin Secretion in Human: Potential Anti-Diabetic Effect of the Drug

Effect of Tianeptine on Glucose Tolerance with Insulin Secretion in Human: Potential Anti-Diabetic Effect of the Drug

Regulation by Glucose of Oscillatory Electrical Activity and 5-HT/Insulin Release from Single Mouse Pancreatic Islets in Absence of Functional KATP Channels

Protein kinase C

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