scholarly journals In pursuit of ryanodine receptors gating in the plasma membrane of RINm5F pancreatic β-cells

Islets ◽  
2009 ◽  
Vol 1 (1) ◽  
pp. 84-86 ◽  
Author(s):  
Rebecca Sitsapesan
Keyword(s):  
Plasma Membrane ◽  
Ryanodine Receptors ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Functional Ryanodine Receptors in the Plasma Membrane of RINm5F Pancreatic β-Cells

2008 ◽  
Vol 284 (8) ◽  
pp. 5186-5194 ◽  
Author(s):  
Christian Rosker ◽  
Gargi Meur ◽  
Emily J. A. Taylor ◽  
Colin W. Taylor
Keyword(s):  
Plasma Membrane ◽  
Ryanodine Receptors ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane

2013 ◽  
Vol 24 (3) ◽  
pp. 319-330 ◽  
Author(s):  
Hao Wang ◽  
Ray Ishizaki ◽  
Jun Xu ◽  
Kazuo Kasai ◽  
Eri Kobayashi ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Knockout Mice ◽  
Secretory Granules ◽  
Small Gtpase ◽  
Membrane Phospholipids ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Insulin Granules ◽  
Insulin Exocytosis

Granuphilin, an effector of the small GTPase Rab27a, mediates the stable attachment (docking) of insulin granules to the plasma membrane and inhibits subsequent fusion of docked granules, possibly through interaction with a fusion-inhibitory Munc18-1/syntaxin complex. However, phenotypes of insulin exocytosis differ considerably between Rab27a- and granuphilin-deficient pancreatic β cells, suggesting that other Rab27a effectors function in those cells. We found that one of the putative Rab27a effector family proteins, exophilin7/JFC1/Slp1, is expressed in β cells; however, unlike granuphilin, exophilin7 overexpressed in the β-cell line MIN6 failed to show granule-docking or fusion-inhibitory activity. Furthermore, exophilin7 has no affinities to either Munc18-1 or Munc18-1–interacting syntaxin-1a, in contrast to granuphilin. Although β cells of exophilin7-knockout mice show no apparent abnormalities in intracellular distribution or in ordinary glucose-induced exocytosis of insulin granules, they do show impaired fusion in response to some stronger stimuli, specifically from granules that have not been docked to the plasma membrane. Exophilin7 appears to mediate the fusion of undocked granules through the affinity of its C2A domain toward the plasma membrane phospholipids. These findings indicate that the two Rab27a effectors, granuphilin and exophilin7, differentially regulate the exocytosis of either stably or minimally docked granules, respectively.

The Ins and Outs of Secretion from Pancreatic β-Cells: Control of Single-Vesicle Exo- and Endocytosis

Physiology ◽  
2007 ◽  
Vol 22 (2) ◽  
pp. 113-121 ◽  
Author(s):  
Patrick E. MacDonald ◽  
Patrik Rorsman
Keyword(s):  
Plasma Membrane ◽  
Plasma Glucose ◽  
Secretory Vesicles ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucose Levels ◽  
Single Vesicle

Exocytosis of insulin-containing secretory vesicles in pancreatic β-cells is crucial to maintenance of plasma glucose levels. They fuse with the plasma membrane in a regulated manner to release their contents and are subsequently recaptured either intact or through conventional clathrin-mediated endocytosis. Here, we discuss these mechanisms in β-cells at the single-vesicle level.

Modeling of Ca2+ flux in pancreatic β-cells: role of the plasma membrane and intracellular stores

2003 ◽  
Vol 285 (1) ◽  
pp. E138-E154 ◽  
Author(s):  
Leonid E. Fridlyand ◽  
Natalia Tamarina ◽  
Louis H. Philipson
Keyword(s):  
Plasma Membrane ◽  
Calcium Oscillations ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Ionic Flux ◽  
Inositol 1,4,5 Trisphosphate ◽  
Intracellular Ca ◽  
Uptake And Release

We have developed a detailed mathematical model of ionic flux in β-cells that includes the most essential channels and pumps in the plasma membrane. This model is coupled to equations describing Ca2+, inositol 1,4,5-trisphosphate (IP3), ATP, and Na+ homeostasis, including the uptake and release of Ca2+ by the endoplasmic reticulum (ER). In our model, metabolically derived ATP activates inward Ca2+ flux by regulation of ATP-sensitive K+ channels and depolarization of the plasma membrane. Results from the simulations support the hypothesis that intracellular Na+ and Ca2+ in the ER can be the main variables driving both fast (2–7 osc/min) and slow intracellular Ca2+ concentration oscillations (0.3–0.9 osc/min) and that the effect of IP3 on Ca2+ leak from the ER contributes to the pattern of slow calcium oscillations. Simulations also show that filling the ER Ca2+ stores leads to faster electrical bursting and Ca2+ oscillations. Specific Ca2+ oscillations in isolated β-cell lines can also be simulated.

scholarly journals Melanophilin accelerates insulin granule fusion without predocking to the plasma membrane

2020 ◽  
Author(s):  
Ada Admin ◽  
Hao Wang ◽  
Kouichi Mizuno ◽  
Noriko Takahashi ◽  
Eri Kobayashi ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Secretory Granule ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Granule Exocytosis ◽  
Synaptic Vesicle Exocytosis ◽  
Granule Membrane ◽  
Myosin Va ◽  
Vesicle Exocytosis ◽  
Glucose Stimulated Insulin Secretion

Direct observation of fluorescence-labeled secretory granule exocytosis in living pancreatic β cells has revealed heterogeneous prefusion behaviors: some granules dwell beneath the plasma membrane before fusion, while others fuse immediately once they are recruited to the plasma membrane. Although the former mode seems to follow sequential docking-priming-fusion steps as found in synaptic vesicle exocytosis, the latter mode, which is unique to secretory granule exocytosis, has not been explored well. Here, we show that melanophilin, one of the effectors of the monomeric GTPase Rab27 on the granule membrane, is involved in such an accelerated mode of exocytosis. Both melanophilin-mutated <i>leaden</i> mouse and melanophilin-downregulated human pancreatic β cells exhibit impaired glucose-stimulated insulin secretion, with a specific reduction in fusion events that bypass stable docking to the plasma membrane. Upon stimulus-induced [Ca<sup>2+</sup>]<sub>i</sub> rise, melanophilin mediates this type of fusion by dissociating granules from myosin-Va and actin in the actin cortex and by associating them with a fusion-competent, open form of syntaxin-4 on the plasma membrane. These findings provide the hitherto unknown mechanism to support sustainable exocytosis by which granules are recruited from the cell interior and fuse promptly without stable predocking to the plasma membrane.

scholarly journals Plasma Membrane Phosphatidylinositol 4,5-Bisphosphate Regulates Ca 2+ -Influx and Insulin Secretion from Pancreatic β Cells

2016 ◽  
Vol 23 (7) ◽  
pp. 816-826 ◽  
Author(s):  
Beichen Xie ◽  
Phuoc My Nguyen ◽  
Alenka Guček ◽  
Antje Thonig ◽  
Sebastian Barg ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Insulin Secretion ◽  
Β Cells ◽  
Pancreatic Β Cells

Contribution of the endoplasmic reticulum to the glucose-induced [Ca2+]c response in mouse pancreatic islets

2002 ◽  
Vol 282 (5) ◽  
pp. E982-E991 ◽  
Author(s):  
Abdelilah Arredouani ◽  
Jean-Claude Henquin ◽  
Patrick Gilon
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Membrane Potential ◽  
Glucose Concentration ◽  
Buffering Capacity ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucose Stimulation ◽  
Mouse Pancreatic Islets ◽  
Fast Oscillations

Thapsigargin (TG), a blocker of Ca2+ uptake by the endoplasmic reticulum (ER), was used to evaluate the contribution of the organelle to the oscillations of cytosolic Ca2+ concentration ([Ca2+]c) induced by repetitive Ca2+ influx in mouse pancreatic β-cells. Because TG depolarized the plasma membrane in the presence of glucose alone, extracellular K+ was alternated between 10 and 30 mM in the presence of diazoxide to impose membrane potential (MP) oscillations. In control islets, pulses of K+, mimicking regular MP oscillations elicited by 10 mM glucose, induced [Ca2+]c oscillations whose nadir remained higher than basal [Ca2+]c. Increasing the depolarization phase of the pulses while keeping their frequency constant (to mimic the effects of a further rise of the glucose concentration on MP) caused an upward shift of the nadir of [Ca2+]c oscillations that was reproduced by raising extracellular Ca2+ (to increase Ca2+influx) without changing the pulse protocol. In TG-pretreated islets, the imposed [Ca2+]c oscillations were of much larger amplitude than in control islets and occurred on basal levels. During intermittent trains of depolarizations, control islets displayed mixed [Ca2+]c oscillations characterized by a summation of fast oscillations on top of slow ones, whereas no progressive summation of the fast oscillations was observed in TG-pretreated islets. In conclusion, the buffering capacity of the ER in pancreatic β-cells limits the amplitude of [Ca2+]c oscillations and may explain how the nadir between oscillations remains above baseline during regular oscillations or gradually increases during mixed [Ca2+]c oscillations, two types of response observed during glucose stimulation.

scholarly journals Cytoprotective Effects of Polyenoylphosphatidylcholine (PPC) on β-cells During Diabetic Induction by Streptozotocin

2003 ◽  
Vol 51 (8) ◽  
pp. 1005-1015 ◽  
Author(s):  
Seung-Hee Lee ◽  
Yu-Mi Han ◽  
Bon-Hong Min ◽  
In-Sun Park
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Glucose Metabolism ◽  
Glucose Homeostasis ◽  
Rapid Recovery ◽  
Cytoprotective Effect ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Insulin Synthesis ◽  
Normal Glucose

Polyenoylphosphatidylcholine (PPC), a phosphatidylcholine-rich phospholipid extracted from soybean, has been reported to protect liver cells from alloxan-induced cytotoxicity. The present study aimed to investigate whether PPC protects pancreatic β-cells from the cytotoxic injury induced by streptozotocin, thus preserving insulin synthesis and secretion. β-Cells of the PPC-treated rats showed a significant reduction of cell death with lesser destruction of plasma membrane on streptozotocin insult. They demonstrated a rapid recovery of GLUT-2 expression, whereas almost irreversible depletion of membranebound GLUT-2 was seen in β-cells of the rats treated with only streptozotocin. A similar cytoprotective effect of PPC was also monitored in the PPC-pretreated MIN6 cells. These β-cells retained their ability to synthesize and secrete insulin and no alteration of glucose metabolism was detected. These results strongly suggest that PPC plays important roles not only in protecting β-cells against cytotoxicity but also in maintaining their insulin synthesis and secretion for normal glucose homeostasis.

Ryanodine receptors of pancreatic β‐cells mediate a distinct context‐dependent signal for insulin secretion

2002 ◽  
Vol 17 (2) ◽  
pp. 301-303 ◽  
Author(s):  
Joseph D. Bruton ◽  
Raf Lemmens ◽  
Chun‐Liang Shi ◽  
Solveig Persson‐Sjögren ◽  
Håkan Westerblad ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Ryanodine Receptors ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Dependent Signal ◽  
Context Dependent

scholarly journals TIRF imaging of docking and fusion of single insulin granule motion in primary rat pancreatic β-cells: different behaviour of granule motion between normal and Goto–Kakizaki diabetic rat β-cells

2004 ◽  
Vol 381 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Mica OHARA-IMAIZUMI ◽  
Chiyono NISHIWAKI ◽  
Toshiteru KIKUTA ◽  
Shintaro NAGAI ◽  
Yoko NAKAMICHI ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Insulin Release ◽  
Secretory Granules ◽  
Dynamic Change ◽  
Second Phase ◽  
Β Cells ◽  
Gk Rat ◽  
Pancreatic Β Cells ◽  
Insulin Granules ◽  
Granule Motion

We imaged and analysed the motion of single insulin secretory granules near the plasma membrane in live pancreatic β-cells, from normal and diabetic Goto–Kakizaki (GK) rats, using total internal reflection fluorescence microscopy (TIRFM). In normal rat primary β-cells, the granules that were fusing during the first phase originate from previously docked granules, and those during the second phase originate from ‘newcomers’. In diabetic GK rat β-cells, the number of fusion events from previously docked granules were markedly reduced, and, in contrast, the fusion from newcomers was still preserved. The dynamic change in the number of docked insulin granules showed that, in GK rat β-cells, the total number of docked insulin granules was markedly decreased to 35% of the initial number after glucose stimulation. Immunohistochemistry with anti-insulin antibody observed by TIRFM showed that GK rat β-cells had a marked decline of endogenous insulin granules docked to the plasma membrane. Thus our results indicate that the decreased number of docked insulin granules accounts for the impaired insulin release during the first phase of insulin release in diabetic GK rat β-cells.

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