ATP Regulates Sodium Channel Kinetics in Pancreatic Islet Beta Cells

Zou, Na; Wu, Xiao Dong; Jin, Yanyan; He, Mai; Wang, Xinxin; Su, Li-Da; Rupnik, Marjan Slak; Wu, Zhenyong; Li, Liang; Shen, Ying

doi:10.1007/s00232-012-9506-7

Cited by 16 publications

(17 citation statements)

References 28 publications

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Section: Nav Channels Modulation By Endogenous Moleculesmentioning

confidence: 99%

“…It was proposed that Na 1 currents may be enhanced by an increase in glucose levels and further ATP production in beta cells (Zou et al, 2013). This idea is supported by whole cell recordings of beta cells in slices from rat pancreas, where concentrations of ATP (2-8 mM) in the recording pipette shift the inactivation curve to more positive potentials and accelerate the recovery from inactivation of VGSC (Zou et al, 2013). In the other direction, the TTXsensitive depolarizing Na 1 influx contributes to the cytosolic Na 1 transients (Nita et al, 2014), which, together with Ca 21 transients, propagate to the mitochondria and modulate ATP synthesis.…”

Section: Nav Channels Modulation By Endogenous Moleculesmentioning

confidence: 99%

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Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

et al. 2016

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Pancreatic beta cells, unique cells that secrete insulin in response to an increase in glucose levels, play a significant role in glucose homeostasis. Glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells has been extensively explored. In this mechanism, glucose enters the cells and subsequently the metabolic cycle. During this process, the ATP/ADP ratio increases, leading to ATP-sensitive potassium (K ATP ) channel closure, which initiates depolarization that is also dependent on the activity of TRP nonselective ion channels. Depolarization leads to the opening of voltage-gated Na 1 channels (Nav) and subsequently voltage-dependent Ca 21 channels (Cav).The increase in intracellular Ca 21 triggers the exocytosis of insulin-containing vesicles. Thus, electrical activity of pancreatic beta cells plays a central role in GSIS. Moreover, many growth factors, incretins, neurotransmitters, and hormones can modulate GSIS, and the channels that participate in GSIS are highly regulated. In this review, we focus on the principal ionic channels (K ATP , Nav, and Cav channels) involved in GSIS and how classic and new proteins, hormones, and drugs regulate it. Moreover, we also discuss advances on how metabolic disorders such as metabolic syndrome and diabetes mellitus change channel activity leading to changes in insulin secretion.

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Section: Nav Channels Modulation By Endogenous Moleculesmentioning

confidence: 99%

Section: Nav Channels Modulation By Endogenous Moleculesmentioning

confidence: 99%

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

et al. 2016

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“…Pancreatic β-cells act as glucose sensors, where intracellular ATP is altered with glucose concentration change. It has been reported that elevated cytosolic ATP enhanced the activity of Na + channels, which lead to modulation of β-cell excitability and insulin release when blood glucose concentration increases [621]. There also appear to be significant species differences.…”

Section: β-Cellsmentioning

confidence: 99%

Purinergic signalling in endocrine organs

Burnstock

2013

Purinergic Signalling

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There is widespread involvement of purinergic signalling in endocrine biology. Pituitary cells express P1, P2X and P2Y receptor subtypes to mediate hormone release. Adenosine 5′-triphosphate (ATP) regulates insulin release in the pancreas and is involved in the secretion of thyroid hormones. ATP plays a major role in the synthesis, storage and release of catecholamines from the adrenal gland. In the ovary purinoceptors mediate gonadotrophin-induced progesterone secretion, while in the testes, both Sertoli and Leydig cells express purinoceptors that mediate secretion of oestradiol and testosterone, respectively. ATP released as a cotransmitter with noradrenaline is involved in activities of the pineal gland and in the neuroendocrine control of the thymus. In the hypothalamus, ATP and adenosine stimulate or modulate the release of luteinising hormone-releasing hormone, as well as arginine-vasopressin and oxytocin. Functionally active P2X and P2Y receptors have been identified on human placental syncytiotrophoblast cells and on neuroendocrine cells in the lung, skin, prostate and intestine. Adipocytes have been recognised recently to have endocrine function involving purinoceptors.

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“…Although α-and β-cells express the same K ATP channels, the activity is lower in α-cells [24]. In β-cells, Ca 2 + currents dominate electrophysiological activity during exocytosis [25]. In α-cells, although Ca 2 + current is detectable, it only comprises 15 % of the magnitude of the Na + current [26,27].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the malate–aspartate shuttle in mouse pancreatic islets abolishes glucagon secretion without affecting insulin secretion

Stamenkovic

Andersson

Adriaenssens

et al. 2015

Biochemical Journal

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Altered secretion of insulin as well as glucagon has been implicated in the pathogenesis of Type 2 diabetes (T2D), but the mechanisms controlling glucagon secretion from α-cells largely remain unresolved. Therefore, we studied the regulation of glucagon secretion from αTC1-6 (αTC1 clone 6) cells and compared it with insulin release from INS-1 832/13 cells. We found that INS-1 832/13 and αTC1-6 cells respectively secreted insulin and glucagon concentration-dependently in response to glucose. In contrast, tight coupling of glycolytic and mitochondrial metabolism was observed only in INS-1 832/13 cells. Although glycolytic metabolism was similar in the two cell lines, TCA (tricarboxylic acid) cycle metabolism, respiration and ATP levels were less glucose-responsive in αTC1-6 cells. Inhibition of the malate-aspartate shuttle, using phenyl succinate (PhS), abolished glucose-provoked ATP production and hormone secretion from αTC1-6 but not INS-1 832/13 cells. Blocking the malate-aspartate shuttle increased levels of glycerol 3-phosphate only in INS-1 832/13 cells. Accordingly, relative expression of constituents in the glycerol phosphate shuttle compared with malate-aspartate shuttle was lower in αTC1-6 cells. Our data suggest that the glycerol phosphate shuttle augments the malate-aspartate shuttle in INS-1 832/13 but not αTC1-6 cells. These results were confirmed in mouse islets, where PhS abrogated secretion of glucagon but not insulin. Furthermore, expression of the rate-limiting enzyme of the glycerol phosphate shuttle was higher in sorted primary β-than in α-cells. Thus, suppressed glycerol phosphate shuttle activity in the α-cell may prevent a high rate of glycolysis and consequently glucagon secretion in response to glucose. Accordingly, pyruvate-and lactate-elicited glucagon secretion remains unaffected since their signalling is independent of mitochondrial shuttles.

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ATP Regulates Sodium Channel Kinetics in Pancreatic Islet Beta Cells

Cited by 16 publications

References 28 publications

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

Purinergic signalling in endocrine organs

Inhibition of the malate–aspartate shuttle in mouse pancreatic islets abolishes glucagon secretion without affecting insulin secretion

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