Electrophysiological characterization of pancreatic islet cells in the mouse insulin promoter-green fluorescent protein mouse

Endocrinology. 2005 Nov;146(11):4766-75. doi: 10.1210/en.2005-0803. Epub 2005 Aug 18.


We recently reported a transgenic [mouse insulin promoter (MIP)-green fluorescent protein (GFP)] mouse in which GFP expression is targeted to the pancreatic islet beta-cells to enable convenient identification of beta-cells as green cells. The GFP-expressing beta-cells of the MIP-GFP mouse were functionally indistinguishable from beta-cells of normal mice. Here we characterized the ionic channel properties and exocytosis of MIP-GFP mouse islet beta- and alpha-cells. Beta-cells displayed delayed rectifying K+ and high-voltage-activated Ca2+ channels and exhibited Na+ currents only at hyperpolarized holding potential. Alpha-cells were nongreen and had both A-type and delayed rectifier K+ channels, both low-voltage-activated and high-voltage-activated Ca2+ channels, and displayed Na+ currents readily at -70 mV holding potential. Alpha-cells had ATP-sensitive K+ channel (KATP) channel density as high as that in beta-cells, and, surprisingly, alpha-cell KATP channels were more sensitive to ATP inhibition (IC50=0.16+/-0.03 mM) than beta-cell KATP channels (IC50=0.86+/-0.10 mM). Whereas alpha-cells were rather uniform in size [2-4.5 picofarad (pF)], beta-cells varied vastly in size (2-12 pF). Of note, small beta-cells (<4.5 pF) showed little exocytosis, whereas medium beta-cells (5-8 pF) exhibited vigorous exocytosis, but large beta-cells (>8 pF) had weaker exocytosis. We found no correlation between beta-cell size and their Ca2+ channel density, suggesting that Ca2+ influx may not be the cause of the heterogeneity in exocytotic responses. The MIP-GFP mouse therefore offers potential to further explore the functional heterogeneity in beta-cells of different sizes. The MIP-GFP mouse islet is therefore a reliable model to efficiently examine alpha-cell and beta-cell physiology and should greatly facilitate examination of their pathophysiology when the MIP-GFP mice are crossed with diabetic models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Calcium Channels / physiology
  • Electrophysiology
  • Exocytosis
  • Green Fluorescent Proteins / genetics*
  • In Vitro Techniques
  • Insulin / genetics*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology*
  • Mice
  • Mice, Transgenic / physiology*
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Potassium Channels / drug effects
  • Potassium Channels / physiology
  • Potassium Channels, Voltage-Gated / physiology
  • Promoter Regions, Genetic*
  • Sodium Channels / physiology


  • Calcium Channels
  • Insulin
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Sodium Channels
  • Green Fluorescent Proteins
  • Adenosine Triphosphate