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首页> 外文期刊>American Journal of Physiology >Identification of the ectonucleotidases expressed in mouse, rat, and human Langerhans islets: potential role of NTPDase3 in insulin secretion.
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Identification of the ectonucleotidases expressed in mouse, rat, and human Langerhans islets: potential role of NTPDase3 in insulin secretion.

机译：鉴定在小鼠，大鼠和人Langerhans胰岛中表达的外切核苷酸酶：NTPDase3在胰岛素分泌中的潜在作用。

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摘要

Extracellular nucleotides and adenosine regulate endocrine pancreatic functions such as insulin secretion by Langerhans islet beta-cells via the activation of specific P2 and P1 receptors. Membrane-bound ectonucleotidases regulate the local concentration of these ligands and consequently control the activation of their receptors. The objective of this study was to identify and localize the major ectonucleotidases, namely NTPDases and ecto-5'-nucleotidase, present in the endocrine pancreas. In addition, the potential implication of ecto-ATPase activity on insulin secretion was investigated in the rat beta-cell line INS-1 (832/13). The localization of ectonucleotidase activity and protein was carried out in situ by enzyme histochemistry and immunolocalization in mouse, rat, and human pancreas sections. NTPDase1 was localized in all blood vessels and acini, and NTPDase2 was localized in capillaries of Langerhans islets and in peripheral conjunctive tissue, whereas NTPDase3 was detected in all Langerhans islet cell types. Interestingly, among the mammalian species tested, ecto-5'-nucleotidase was present only in rat Langerhans islet cells, where it was coexpressed with NTPDase3. Notably, the inhibition of NTPDase3 activity by BG0136 and NF279 facilitated insulin release from INS-1 (832/13) cells under conditions of low glycemia, probably by affecting P2 receptor activation. NTPDase3 activity also regulated the inhibitory effect of exogenous ATP in the presence of a high glucose concentration most likely by controlling adenosine production. In conclusion, all pancreatic endocrine cells express NTPDase3 that was shown to modulate insulin secretion in rat INS-1 (832/13) beta-cells. Ecto-5'-nucleotidase is expressed in rat Langerhans islet cells but absent in human and mouse endocrine cells.
机译：细胞外核苷酸和腺苷通过激活特定的P2和P1受体来调节内分泌胰腺功能，例如Langerhans胰岛β细胞分泌胰岛素。膜结合的外切核苷酸酶调节这些配体的局部浓度，并因此控制其受体的活化。这项研究的目的是鉴定和定位存在于内分泌胰腺中的主要胞外核苷酸酶，即NTPDase和ecto-5'-核苷酸酶。另外，在大鼠β-细胞系INS-1（832/13）中研究了胞外ATPase活性对胰岛素分泌的潜在影响。胞外核苷酸酶活性和蛋白质的定位通过酶组织化学和免疫定位在小鼠，大鼠和人胰腺切片中原位进行。 NTPDase1位于所有血管和腺泡中，NTPDase2位于Langerhans胰岛的毛细血管和周围结膜组织中，而NTPDase3在所有Langerhans胰岛细胞类型中均被检测到。有趣的是，在所测试的哺乳动物物种中，ecto-5'-核苷酸酶仅存在于大鼠Langerhans胰岛细胞中，并与NTPDase3共表达。值得注意的是，在低血糖条件下，BG0136和NF279对NTPDase3活性的抑制作用促进了胰岛素从INS-1（832/13）细胞的释放，可能是通过影响P2受体的活化来实现的。 NTPDase3活性还可以通过控制腺苷的产生来调节高糖浓度下外源ATP的抑制作用。总之，所有胰腺内分泌细胞均表达NTPDase3，NTPDase3可以调节大鼠INS-1（832/13）β细胞中的胰岛素分泌。 Ecto-5'-核苷酸酶在大鼠Langerhans胰岛细胞中表达，但在人和小鼠内分泌细胞中不存在。

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