scholarly journals Cyanidin-3-rutinoside stimulated insulin secretion through activation of L-type voltage-dependent Ca2+ channels and the PLC-IP3 pathway in pancreatic β-cells

2022 ◽  
Vol 146 ◽  
pp. 112494
Author(s):  
Phutthida Kongthitilerd ◽  
Thavaree Thilavech ◽  
Marisa Marnpae ◽  
Weiqiong Rong ◽  
Shaomian Yao ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Voltage Dependent ◽  
Ca2 Channels

scholarly journals Protein Kinase CK2 Controls CaV2.1-Dependent Calcium Currents and Insulin Release in Pancreatic β-cells

2020 ◽  
Vol 21 (13) ◽  
pp. 4668
Author(s):  
Rebecca Scheuer ◽  
Stephan Ernst Philipp ◽  
Alexander Becker ◽  
Lisa Nalbach ◽  
Emmanuel Ampofo ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Calcium Currents ◽  
Insulin Biosynthesis ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Voltage Dependent ◽  
Regulatory Impact ◽  
Kinase Ck2

The regulation of insulin biosynthesis and secretion in pancreatic β-cells is essential for glucose homeostasis in humans. Previous findings point to the highly conserved, ubiquitously expressed serine/threonine kinase CK2 as having a negative regulatory impact on this regulation. In the cell culture model of rat pancreatic β-cells INS-1, insulin secretion is enhanced after CK2 inhibition. This enhancement is preceded by a rise in the cytosolic Ca2+ concentration. Here, we identified the serine residues S2362 and S2364 of the voltage-dependent calcium channel CaV2.1 as targets of CK2 phosphorylation. Furthermore, co-immunoprecipitation experiments revealed that CaV2.1 binds to CK2 in vitro and in vivo. CaV2.1 knockdown experiments showed that the increase in the intracellular Ca2+ concentration, followed by an enhanced insulin secretion upon CK2 inhibition, is due to a Ca2+ influx through CaV2.1 channels. In summary, our results point to a modulating role of CK2 in the CaV2.1-mediated exocytosis of insulin.

scholarly journals N-Type Ca2+-Channels in Murine Pancreatic β-Cells Are Inhibited by an Exclusive Coupling with Somatostatin Receptor Subtype 1

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 741-748 ◽  
Author(s):  
Paul A. Smith
Keyword(s):  
Insulin Secretion ◽  
Somatostatin Receptor ◽  
Inhibitory Effect ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Somatostatin Receptor Subtypes ◽  
Perforated Patch Clamp ◽  
Ca2 Channels

Somatostatin (SRIF) is a well-established inhibitor of insulin secretion, an effect in part mediated by a direct inhibition of voltage-operated Ca2+-channels. However, the identity of the somatostatin receptor subtypes (SSTRs) and voltage-operated Ca2+-channels involved in this process are unknown. Whole-cell perforated patch-clamp methods were applied to the murine pancreatic β-cell line, MIN6, to explore the molecular pharmacology of this problem. SRIF-14 inhibited voltage-gated Ca2+ currents (ICa2+) by 19 ± 3% (n=24) with a pEC50 = 9.05 (95% confidence limits 9–9.1). This action was mimicked solely by 100 nm CH-275, a selective agonist at the somatostatin type 1 receptor (SSTR1), but not by 100 nm BIM-23027, L-362855, or NNC-269100; agonists selective for the other four SSTRs known to exist in MIN6. The inhibition of ICa2+ produced by SRIF and CH-275 was insensitive to pertussis toxin but was reversed by a prepulse to +100 mV. The inhibition of ICa2+ by SRIF-14 was unaffected by 20 μm nifedipine, an inhibitor of L-type Ca2+ channels. Application of the specific N-type Ca2+ channel (Cav2.2) inhibitor ω-conotoxin GV1A at 100 nm mimicked, and as a consequence abolished, the inhibitory effect of SRIF-14 on ICa2+. SRIF selectively inhibits N-type Ca2+-channels in murine pancreatic β-cells via exclusive coupling with SSTR1. These findings help explain how SSTR1 activation can inhibit insulin secretion in pancreatic β-cells and suggest a possible new therapeutic lead for treatment of hyperinsulinemia. In pancreatic β-cells, somatostatin selectively inhibits N-type, but not other, Ca2+-channels via a direct and exclusive coupling with somatostatin receptor subtype 1.

scholarly journals Propofol inhibits stromatoxin-1-sensitive voltage-dependent K+ channels in pancreatic β-cells and enhances insulin secretion

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8157 ◽  
Author(s):  
Munenori Kusunoki ◽  
Mikio Hayashi ◽  
Tomohiro Shoji ◽  
Takeo Uba ◽  
Hiromasa Tanaka ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Energy Metabolism ◽  
Glycemic Control ◽  
Potassium Channels ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Kv Channels ◽  
Voltage Dependent ◽  
Cellular Oxygen ◽  
Low Glucose

Background Proper glycemic control is an important goal of critical care medicine, including perioperative patient care that can influence patients’ prognosis. Insulin secretion from pancreatic β-cells is generally assumed to play a critical role in glycemic control in response to an elevated blood glucose concentration. Many animal and human studies have demonstrated that perioperative drugs, including volatile anesthetics, have an impact on glucose-stimulated insulin secretion (GSIS). However, the effects of the intravenous anesthetic propofol on glucose metabolism and insulin sensitivity are largely unknown at present. Methods The effect of propofol on insulin secretion under low glucose or high glucose was examined in mouse MIN6 cells, rat INS-1 cells, and mouse pancreatic β-cells/islets. Cellular oxygen or energy metabolism was measured by Extracellular Flux Analyzer. Expression of glucose transporter 2 (GLUT2), potassium channels, and insulin mRNA was assessed by qRT-PCR. Protein expression of voltage-dependent potassium channels (Kv2) was also assessed by immunoblot. Propofol’s effects on potassium channels including stromatoxin-1-sensitive Kv channels and cellular oxygen and energy metabolisms were also examined. Results We showed that propofol, at clinically relevant doses, facilitates insulin secretion under low glucose conditions and GSIS in MIN6, INS-1 cells, and pancreatic β-cells/islets. Propofol did not affect intracellular ATP or ADP concentrations and cellular oxygen or energy metabolism. The mRNA expression of GLUT2 and channels including the voltage-dependent calcium channels Cav1.2, Kir6.2, and SUR1 subunit of KATP, and Kv2 were not affected by glucose or propofol. Finally, we demonstrated that propofol specifically blocks Kv currents in β-cells, resulting in insulin secretion in the presence of glucose. Conclusions Our data support the hypothesis that glucose induces membrane depolarization at the distal site, leading to KATP channel closure, and that the closure of Kv channels by propofol depolarization in β-cells enhances Ca2+ entry, leading to insulin secretion. Because its activity is dependent on GSIS, propofol and its derivatives are potential compounds that enhance and initiate β-cell electrical activity.

scholarly journals Intracellular ATP Signaling Contributes to FAM3A-Induced PDX1 Upregulation in Pancreatic Beta Cells

2021 ◽  
Author(s):  
Han Yan ◽  
Zhenzhen Chen ◽  
Haizeng Zhang ◽  
Weili Yang ◽  
Xiangyang Liu ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Beta Cells ◽  
Mitochondrial Protein ◽  
Extracellular Atp ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Intracellular Atp ◽  
Pdx1 Expression ◽  
Ca2 Channels

AbstractFAM3A is a recently identified mitochondrial protein that stimulates pancreatic-duodenal homeobox 1 (PDX1) and insulin expressions by promoting ATP release in islet β cells. In this study, the role of intracellular ATP in FAM3A-induced PDX1 expression in pancreatic β cells was further examined. Acute FAM3A inhibition using siRNA transfection in mouse pancreatic islets significantly reduced PDX1 expression, impaired insulin secretion, and caused glucose intolerance in normal mice. In vitro, FAM3A overexpression elevated both intracellular and extracellular ATP contents and promoted PDX1 expression and insulin secretion. FAM3A-induced increase in cellular calcium (Ca2+) levels, PDX1 expression, and insulin secretion, while these were significantly repressed by inhibitors of P2 receptors or the L-type Ca2+ channels. FAM3A-induced PDX1 expression was abolished by a calmodulin inhibitor. Likewise, FAM3A-induced β-cell proliferation was also inhibited by a P2 receptor inhibitor and an L-type Ca2+ channels inhibitor. Both intracellular and extracellular ATP contributed to FAM3A-induced PDX1 expression, insulin secretion, and proliferation of pancreatic β cells.

scholarly journals Linoleic acid induces Ca2+-induced inactivation of voltage-dependent Ca2+ currents in rat pancreatic β-cells

2007 ◽  
Vol 196 (2) ◽  
pp. 377-384 ◽  
Author(s):  
Dan-Dan Feng ◽  
Yu-Feng Zhao ◽  
Zi-Qiang Luo ◽  
Damien J Keating ◽  
Chen Chen
Keyword(s):  
Insulin Secretion ◽  
Linoleic Acid ◽  
Specific Protein ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Cell Dysfunction ◽  
Cell Recording ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
G Protein Coupled

Free fatty acids (FFAs) regulate insulin secretion in a complex pattern and induce pancreatic β-cell dysfunction in type 2 diabetes. Voltage-dependent Ca2+ channels (VDCC) in β-cells play a major role in regulating insulin secretion. The aim of present study is to clarify the action of the FFA, linoleic acid, on VDCC in β-cells. The VDCC current in primary cultured rat β-cells were recorded under nystatin-perforated whole-cell recording configuration. The VDCC was identified as high-voltage-gated Ca2+ channels due to there being no difference in current amplitude under holding potential between −70 and −40 mV. Linoleic acid (10 μM) significantly inhibited VDCC currents in β-cells, an effect which was fully reversible upon washout. Methyl-linoleic acid, which does not activate G protein coupled receptor (GPR)40, neither did alter VDCC current in rat β-cells nor did influence linoleic acid-induced inhibition of VDCC currents. Linoleic acid-induced inhibition of VDCC current was not blocked by preincubation of β-cells with either the specific protein kinase A (PKA) inhibitor, H89, or the PKC inhibitor, chelerythrine. However, pretreatment of β-cells with thapsigargin, which depletes intracellular Ca2+ stores, completely abolished linoleic acid-induced decrease in VDCC current. Measurement of intracellular Ca2+ concentration ([Ca2+]i) illustrated that linoleic acid induced an increase in [Ca2+]i and that thapsigargin pretreatment inhibited this increase. Methyl-linoleic acid neither did induce increase in [Ca2+]i nor did it block linoleic acid-induced increase in [Ca2+]i. These results suggest that linoleic acid stimulates Ca2+ release from intracellular Ca2+ stores and inhibits VDCC currents in rat pancreatic β-cells via Ca2+-induced inactivation of VDCC.

scholarly journals Inhibition of voltage-dependent potassium channels mediates cAMP-potentiated insulin secretion in rat pancreatic β cells

Islets ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 11-18 ◽  
Author(s):  
Yunfeng Liu ◽  
Xiangqin Zhong ◽  
Yaqin Ding ◽  
Lele Ren ◽  
Tao Bai ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Potassium Channels ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Voltage Dependent

Involvement of stretch-activated cation channels in hypotonically induced insulin secretion in rat pancreatic β-cells

2006 ◽  
Vol 291 (6) ◽  
pp. C1405-C1411 ◽  
Author(s):  
Miki Takii ◽  
Tomohisa Ishikawa ◽  
Hidetaka Tsuda ◽  
Kazumitsu Kanatani ◽  
Takaaki Sunouchi ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Membrane Depolarization ◽  
Ruthenium Red ◽  
Cell Swelling ◽  
Cation Channels ◽  
Channel Blockers ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Voltage Dependent ◽  
Isolated Rat

In isolated rat pancreatic β-cells, hypotonic stimulation elicited an increase in cytosolic Ca2+ concentration ([Ca2+]c) at 2.8 mM glucose. The hypotonically induced [Ca2+]c elevation was significantly suppressed by nicardipine, a voltage-dependent Ca2+ channel blocker, and by Gd3+, amiloride, 2-aminoethoxydiphenylborate, and ruthenium red, all cation channel blockers. In contrast, the [Ca2+]c elevation was not inhibited by suramin, a P2 purinoceptor antagonist. Whole cell patch-clamp analyses showed that hypotonic stimulation induced membrane depolarization of β-cells and produced outwardly rectifying cation currents; Gd3+ inhibited both responses. Hypotonic stimulation also increased insulin secretion from isolated rat islets, and Gd3+ significantly suppressed this secretion. Together, these results suggest that osmotic cell swelling activates cation channels in rat pancreatic β-cells, thereby causing membrane depolarization and subsequent activation of voltage-dependent Ca2+ channels and thus elevating insulin secretion.

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