Electrophysiological characterization of pancreatic islet cells in the mouse insulin promoter-green fluorescent protein mouse
Electrophysiological characterization of pancreatic islet cells in the mouse insulin promoter-green fluorescent protein mouse
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DOI：
10.1210/en.2005-0803
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发表时间：
2005-11-01
期刊：
影响因子：
4.8
通讯作者：
Gaisano, HY
中科院分区：
文献类型：
--
作者：
Leung, YM;Ahmed, I;Gaisano, HY
我们最近报道了一种转基因[小鼠胰岛素启动子（MIP）-绿色荧光蛋白（GFP）]小鼠，其中GFP表达靶向胰岛β-细胞，从而能够方便地将β-细胞鉴定为绿色细胞. MIP-GFP小鼠的GFP表达β细胞与正常小鼠的β细胞在功能上无法区分。在这里，我们表征了MIPGFP小鼠胰岛β细胞和α细胞的离子通道特性和胞吐作用。β-细胞显示延迟整流钾通道和高电压激活的钙通道，仅在超极化保持电位下显示钠电流。α-细胞为非绿色，具有A型和延迟整流型K+通道，低压激活和高压激活的Ca ~（2+）通道，并在-70mV保持电位下容易显示Na ~+电流。α-细胞具有与β-细胞一样高的ATP敏感性K+通道（KATP）通道密度，并且令人惊讶的是，α-细胞K-ATP通道比β-细胞K-ATP通道（IC 50 = 0.86 +/-0.10mM）对ATP抑制更敏感（IC 50 = 0.16 +/-0.03mM）。尽管α细胞的大小相当均匀[ 2 - 4.5皮法（pF）]，β细胞的大小变化很大（2 - 12 pF）.值得注意的是，小β细胞（<4.5pF）显示出很少的胞吐作用，而中等β细胞（5 - 8 pF）显示出强烈的胞吐作用，但大β细胞（> 8 pF）具有较弱的胞吐作用.我们发现β细胞的大小和它们的Ca ~（2+）通道密度之间没有相关性，这表明Ca ~（2+）内流可能不是胞吐反应异质性的原因。因此，MIP-GFP小鼠提供了进一步探索不同大小β细胞功能异质性的潜力.因此，MIP-GFP小鼠胰岛是有效检查α-细胞和β-细胞生理学的可靠模型，并且当MIP-GFP小鼠与糖尿病模型杂交时，应极大地促进其病理生理学的检查.
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 MIPGFP 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 -70mV holding potential. alpha- Cells had ATP- sensitive K+ channel ( KATP) channel density as high as that in beta- cells, and, surprisingly, alpha- cell K-ATP channels were more sensitive ATP inhibition ( IC50 = 0.16 +/- 0.03 mM) than beta- cell K-ATP 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 ound 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.