Voltage-dependent entry and generation of slow Ca2+ oscillations in glucose-stimulated pancreatic β-cells

1999 ◽  
Vol 276 (3) ◽  
pp. E512-E518 ◽  
Author(s):  
Staffan Dryselius ◽  
Eva Grapengiesser ◽  
Bo Hellman ◽  
Erik Gylfe
Keyword(s):  
Pancreatic Islets ◽  
Glucose Concentration ◽  
Similar Relationship ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Slow Oscillations ◽  
Voltage Dependent ◽  
Individual Mouse

The role of voltage-dependent Ca2+ entry for glucose generation of slow oscillations of the cytoplasmic Ca2+ concentration ([Ca2+]i) was evaluated in individual mouse pancreatic β-cells. Like depolarization with K+, a rise of the glucose concentration resulted in an enhanced influx of Mn2+, which was inhibited by nifedipine. This antagonist of L-type Ca2+ channels also blocked the slow oscillations of [Ca2+]iinduced by glucose. The slow oscillations occurred in synchrony with variations in Mn2+ influx and bursts of action currents, with the elevation of [Ca2+]ibeing proportional to the frequency of the action currents. A similar relationship was obtained when Ca2+ was replaced with Sr2+. Occasionally, the slow [Ca2+]ioscillations were superimposed with pronounced spikes temporarily arresting the action currents. It is concluded that the glucose-induced slow oscillations of [Ca2+]iare caused by periodic depolarization with Ca2+ influx through L-type channels. Ca2+ spiking, due to intracellular mobilization, may be important for chopping the slow oscillations of [Ca2+]iinto shorter ones characterizing β-cells situated in pancreatic islets.

scholarly journals Store-operated influx of Ca2+ in pancreatic β-cells exhibits graded dependence on the filling of the endoplasmic reticulum

2001 ◽  
Vol 114 (11) ◽  
pp. 2179-2186 ◽  
Author(s):  
Oleg Dyachok ◽  
Erik Gylfe
Keyword(s):  
Endoplasmic Reticulum ◽  
Channel Blocker ◽  
Cyclopiazonic Acid ◽  
Atpase Inhibitor ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Rate Of Increase ◽  
Voltage Dependent ◽  
Individual Mouse ◽  
Extracellular Ions

The store-operated pathway for Ca2+ entry was studied in individual mouse pancreatic β-cells by measuring the cytoplasmic concentrations of Ca2+ ([Ca2+]i) and Mn2+ ([Mn2+]i) with the fluorescent indicator fura-2. Influx through the store-operated pathway was initially shut off by pre-exposure to 20 mM glucose, which maximally stimulates intracellular Ca2+ sequestration. To avoid interference with voltage-dependent Ca2+ entry the cells were hyperpolarized with diazoxide and the channel blocker methoxyverapamil was present. Activation of the store-operated pathway in response to Ca2+ depletion of the endoplasmic reticulum was estimated from the sustained elevation of [Ca2+]i or from the rate of increase in [Mn2+]i due to influx of these extracellular ions. Increasing concentrations of the inositol 1,4,5-trisphosphate-generating agonist carbachol or the sarco(endo)plasmatic reticulum Ca2+-ATPase inhibitor cyclopiazonic acid (CPA) cause gradual activation of the store-operated pathway. In addition, the carbachol- and CPA-induced influx of Mn2+ depended on store filling in a graded manner. The store-operated influx of Ca2+/Mn2+ was inhibited by Gd3+ and 2-aminoethoxydiphenyl borate but neither of these agents discriminated between store-operated and voltage-dependent entry. The finely tuned regulation of the store-operated mechanisms in the β-cell has direct implications for the control of membrane potential and insulin secretion.

Non-functional role of syntaxin 2 in insulin exocytosis by pancreatic β cells

1997 ◽  
Vol 15 (4) ◽  
pp. 237-242 ◽  
Author(s):  
Shinya Nagamatsu ◽  
Hiroki Sawa ◽  
Yoko Nakamichi ◽  
Yoshinori Kondo ◽  
Satsuki Matsushima ◽  
...  
Keyword(s):  
Functional Role ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Insulin Exocytosis

Role of Receptor Binding and Gene Transcription for Both of Stimulatory and Inhibitory Effects of Interleukin-1 In Pancreatic β-Cells

Autoimmunity ◽  
1992 ◽  
Vol 12 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Décio L. Eizirik ◽  
Daniel E. Tracey ◽  
Klaus Bendtzen ◽  
Stellan Sandler
Keyword(s):  
Gene Transcription ◽  
Receptor Binding ◽  
Interleukin 1 ◽  
Inhibitory Effects ◽  
Β Cells ◽  
Pancreatic Β Cells

Emerging Role of SUMO in Pancreatic β-Cells

2007 ◽  
Vol 39 (9) ◽  
pp. 658-664 ◽  
Author(s):  
A. Ehninger ◽  
H. Mziaut ◽  
M. Solimena
Keyword(s):  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Role of Nitric Oxide in the Pathogenesis of Encephalomyocarditis Virus-Induced Diabetes in Mice

2009 ◽  
Vol 83 (16) ◽  
pp. 8004-8011 ◽  
Author(s):  
Young-Sun Lee ◽  
Na Li ◽  
Seungjin Shin ◽  
Hee-Sook Jun
Keyword(s):  
Virus Infection ◽  
Encephalomyocarditis Virus ◽  
Wild Type ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Diabetes In Mice ◽  
Tnf Α ◽  
Deficient Mice

ABSTRACT The D variant of encephalomyocarditis virus (EMC-D virus) causes diabetes in mice by destroying pancreatic β cells. In mice infected with a low dose of EMC-D virus, macrophages play an important role in β-cell destruction by producing soluble mediators such as interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and nitric oxide (NO). To investigate the role of NO and inducible NO synthase (iNOS) in the development of diabetes in EMC-D virus-infected mice, we infected iNOS-deficient DBA/2 mice with EMC-D virus (2 × 102 PFU/mouse). Mean blood glucose levels in EMC-D virus-infected iNOS-deficient mice and wild-type mice were 205.5 and 466.7 mg/dl, respectively. Insulitis and macrophage infiltration were reduced in islets of iNOS-deficient mice compared with wild-type mice at 3 days after EMC-D virus infection. Apoptosis of β cells was decreased in iNOS-deficient mice, as evidenced by reduced numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells. There were no differences in mRNA expression of antiapoptotic molecules Bcl-2, Bcl-xL, Bcl-w, Mcl-1, cIAP-1, and cIAP-2 between wild-type and iNOS-deficient mice, whereas expression of proapoptotic Bax and Bak mRNAs was significantly decreased in iNOS-deficient mice. Expression of IL-1β and TNF-α mRNAs was significantly decreased in both islets and macrophages of iNOS-deficient mice compared with wild-type mice after EMC-D virus infection. Nuclear factor κB was less activated in macrophages of iNOS-deficient mice after virus infection. We conclude that NO plays an important role in the activation of macrophages and apoptosis of pancreatic β cells in EMC-D virus-infected mice and that deficient iNOS gene expression inhibits macrophage activation and β-cell apoptosis, contributing to prevention of EMC-D virus-induced diabetes.

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