Charpantier E, Cancela J, Meda P
Department of Cell Physiology and Metabolism, University of Geneva, C.M.U., 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
Diabetologia. 2007 Nov;50(11):2332-41. doi: 10.1007/s00125-007-0807-9. Epub 2007 Sep 8.
AIMS/HYPOTHESIS: Pancreatic beta cells are connected by gap junction channels made of connexin 36 (Cx36), which permit intercellular exchanges of current-carrying ions (ionic coupling) and other molecules (metabolic coupling). Previous studies have suggested that ionic coupling may extend to larger regions of pancreatic islets than metabolic coupling. The aim of the present study was to investigate whether this apparent discrepancy reflects a difference in the sensitivity of the techniques used to evaluate beta cell communication or a specific characteristic of the Cx36 channels themselves.
We microinjected several gap junction tracers, differing in size and charge, into individual insulin-producing cells and evaluated their intercellular exchange either within intact islets of control, knockout and transgenic mice featuring beta cells with various levels of Cx36, or in cultures of wild-type and Cx36-transfected MIN6 cells.
We found that (1) Cx36 channels favour the exchange of cations and larger positively charged molecules between beta cells at the expense of anionic molecules; (2) this exchange occurs across sizable portions of pancreatic islets; and (3) during glibenclamide (known as glyburide in the USA and Canada) stimulation beta cell coupling increases to an extent that varies for different gap junction-permeant molecules.
CONCLUSIONS/INTERPRETATION: The data show that beta cells are extensively coupled within pancreatic islets via exchanges of mostly positively charged molecules across Cx36 channels. These exchanges selectively increase during stimulation of insulin secretion. The identification of this permselectivity is expected to facilitate the identification of endogenous permeant molecules and of the mechanism whereby Cx36 signalling significantly contributes to the modulation of insulin secretion.
目的/假设：胰腺β细胞通过由连接蛋白36（Cx36）构成的缝隙连接通道相连，这些通道允许携带电流的离子进行细胞间交换（离子偶联）以及其他分子进行细胞间交换（代谢偶联）。先前的研究表明，离子偶联可能比代谢偶联扩展到胰岛的更大区域。本研究的目的是调查这种明显的差异是反映了用于评估β细胞通讯的技术敏感性的差异，还是Cx36通道本身的特定特征。
我们将几种大小和电荷不同的缝隙连接示踪剂显微注射到单个产生胰岛素的细胞中，并在完整的对照胰岛、基因敲除胰岛和转基因胰岛中评估它们的细胞间交换，这些胰岛中的β细胞具有不同水平的Cx36，或者在野生型和Cx36转染的MIN6细胞培养物中进行评估。
我们发现：（1）Cx36通道有利于β细胞之间阳离子和较大带正电荷分子的交换，而不利于阴离子分子的交换；（2）这种交换发生在胰岛的相当大的部分；（3）在格列本脲（在美国和加拿大称为优降糖）刺激期间，β细胞偶联增加，其程度因不同的缝隙连接通透分子而异。
结论/解读：数据表明，β细胞通过Cx36通道上主要带正电荷分子的交换在胰岛内广泛偶联。这些交换在胰岛素分泌刺激期间选择性增加。这种通透选择性的确定有望促进内源性通透分子的鉴定以及Cx36信号显著促进胰岛素分泌调节的机制的鉴定。
