Cellular and Molecular Life Sciences

, Volume 71, Issue 21, pp 4149–4177 | Cite as

Ionic mechanisms in pancreatic β cell signaling

  • Shao-Nian YangEmail author
  • Yue Shi
  • Guang Yang
  • Yuxin Li
  • Jia Yu
  • Per-Olof Berggren


The function and survival of pancreatic β cells critically rely on complex electrical signaling systems composed of a series of ionic events, namely fluxes of K+, Na+, Ca2+ and Cl across the β cell membranes. These electrical signaling systems not only sense events occurring in the extracellular space and intracellular milieu of pancreatic islet cells, but also control different β cell activities, most notably glucose-stimulated insulin secretion. Three major ion fluxes including K+ efflux through ATP-sensitive K+ (KATP) channels, the voltage-gated Ca2+ (CaV) channel-mediated Ca2+ influx and K+ efflux through voltage-gated K+ (KV) channels operate in the β cell. These ion fluxes set the resting membrane potential and the shape, rate and pattern of firing of action potentials under different metabolic conditions. The KATP channel-mediated K+ efflux determines the resting membrane potential and keeps the excitability of the β cell at low levels. Ca2+ influx through CaV1 channels, a major type of β cell CaV channels, causes the upstroke or depolarization phase of the action potential and regulates a wide range of β cell functions including the most elementary β cell function, insulin secretion. K+ efflux mediated by KV2.1 delayed rectifier K+ channels, a predominant form of β cell KV channels, brings about the downstroke or repolarization phase of the action potential, which acts as a brake for insulin secretion owing to shutting down the CaV channel-mediated Ca2+ entry. These three ion channel-mediated ion fluxes are the most important ionic events in β cell signaling. This review concisely discusses various ionic mechanisms in β cell signaling and highlights KATP channel-, CaV1 channel- and KV2.1 channel-mediated ion fluxes.


Calcium mobilization Electrophysiology Exocytosis Ion channel Pancreatic endocrine cell Protein kinase 



α1-interaction domain


Cytosolic free Ca2+ concentration


Calcium/calmodulin-dependent kinase II


Voltage-gated Ca2+


CaV1 channel conductance


KATP channel conductance


KV2.1 channel conductance


ATP-sensitive K+


Voltage-gated K+


Potassium inward rectifier


Nucleotide-binding fold


Phosphatidylinositol 4,5-bisphosphate


Protein kinase A


Protein kinase C


Membrane-associated pore loop


Sulfonylurea receptor


Transmembrane domain



Our research was supported by grants from Berth von Kantzow’s Foundation, Diabetes Research and Wellness Foundation, EuroDia (FP6-518153), European Research Council (ERC-2013-AdG), the Family Erling-Persson Foundation, Fredrik and Ingrid Thuring’s Foundation, Funds of Karolinska Institutet, the Knut and Alice Wallenberg Foundation, Magn. Bergvall’s Foundation, Novo Nordisk Foundation, Skandia Insurance Company, Ltd., the Stichting af Jochnick Foundation, Strategic Research Program in Diabetes at Karolinska Institutet, the Swedish Alzheimer Association, the Swedish Diabetes Association, the Swedish Foundation for Strategic Research, the Swedish Research Council, the Swedish Society of Medicine, Torsten and Ragnar Söderberg Foundation, VIBRANT (FP7-228933-2) and Åke Wiberg’s Foundation. P.-O. Berggren is founder of the Biotech Company BioCrine AB and is also a member of the board of this company. S.-N.Yang is a consultant to BioCrine AB. BioCrine AB is developing ApoCIII as a novel druggable target for the treatment of diabetes.


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Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Shao-Nian Yang
    • 1
    • 3
    Email author
  • Yue Shi
    • 1
  • Guang Yang
    • 1
    • 2
  • Yuxin Li
    • 3
  • Jia Yu
    • 1
  • Per-Olof Berggren
    • 1
  1. 1.The Rolf Luft Research Center for Diabetes and EndocrinologyKarolinska InstitutetStockholmSweden
  2. 2.Jilin Academy of Traditional Chinese MedicineChangchunChina
  3. 3.National Engineering Laboratory for Druggable Gene and Protein ScreeningNortheast Normal UniversityChangchunChina

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