Nitric oxide inhibits, and carbon monoxide activates, islet acid α-glucoside hydrolase activities in parallel with glucose-stimulated insulin secretion
Nitric oxide inhibits, and carbon monoxide activates, islet acid α-glucoside hydrolase activities in parallel with glucose-stimulated insulin secretion
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DOI：
10.1677/joe.1.06890
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发表时间：
2006-09-01
影响因子：
4
通讯作者：
Lundquist, Ingmar
中科院分区：
文献类型：
--
作者：
Mosen, Henrik;Salehi, Albert;Lundquist, Ingmar
我们已经研究了一氧化氮（NO）和一氧化碳（CO），假定的信使分子在大脑中，以及在胰岛，对葡萄糖刺激的胰岛素分泌和酸性α-葡萄糖苷水解酶的活性的影响，我们以前已经表明，在胰岛素释放过程中牵连的酶。我们在这里已经表明，外源性NO气体抑制，而CO气体放大葡萄糖刺激的胰岛素分泌在完整的小鼠胰岛伴随着显着的抑制（NO）和显着的激活（CO）的活性的溶酶体/液泡酶酸性葡聚糖-1，4-α-葡萄糖苷酶和酸性α-葡萄糖苷酶（酸性g-葡萄糖苷水解酶）。此外，在0.1-1000 μ M范围内，CO剂量依赖性地增强葡萄糖刺激的胰岛素分泌。在完整的胰岛，血红素加氧酶底物氯化血红素显着放大葡萄糖刺激的胰岛素释放，这是伴随着酸性α-葡萄糖苷水解酶的活性增加的效果。鸟苷酸环化酶抑制剂1H-[1，2，4]恶二唑并[4，3-a]喹喔啉-1-酮可部分抑制上述作用。氯化血红素还抑制诱导型NO合酶。诱导型一氧化氮合酶（iNOS）衍生的NO的生产可能是通过对NOS酶的CO的直接影响。此外，外源性CO提高了cGMP和cAMP的含量与葡萄糖刺激的胰岛素释放的显着放大平行，而外源性NO抑制胰岛素释放和cAMP，使cGMP不受影响。Emiglitate是一种α-葡萄糖苷水解酶活性的选择性抑制剂，它能显著抑制外源性CO对葡萄糖刺激的胰岛素分泌和酸性葡聚糖-1，4-α-葡萄糖苷酶及酸性α-葡萄糖苷酶活性的刺激作用，而对其它溶酶体酶活性无明显影响。两者都在胰岛中大量产生，对葡萄糖刺激的胰岛素分泌具有相互作用的调节作用。这种调节至少部分通过cGMP和溶酶体/空泡系统以及相关的酸性α-葡萄糖苷水解酶的活性转导，但也可能通过对cAMP系统的直接作用。
We have studied the influence of nitric oxide (NO) and carbon monoxide (CO), putative messenger molecules in the brain as well as in the islets of Langerhans, on glucose-stimulated insulin secretion and on the activities of the acid alpha-glucoside hydrolases, enzymes which we previously have shown to be implicated in the insulin release process. We have shown here that exogenous NO gas inhibits, while CO gas amplifies glucose-stimulated insulin secretion in intact mouse islets concomitant with a marked inhibition (NO) and a marked activation (CO) of the activities of the lysosomal/vacuolar enzymes acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase (acid g-glucoside hydrolases). Furthermore, CO dose-dependently potentiated glucose-stimulated insulin secretion in the range 0.1-1000 mu M. In intact islets, the heme oxygenase substrate hemin markedly amplified glucose-stimulated insulin release, an effect which was accompanied by an increased activity of the acid a-glucoside hydrolases. These effects were partially suppressed by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. Hemin also inhibited inducible NO synthase. (iNOS)-derived NO production probably through a direct effect of CO on the NOS enzyme. Further, exogenous CO raised the content of both cGMP and cAMP in parallel with a marked amplification of glucose-stimulated insulin release, while exogenous NO suppressed insulin release and cAMP, leaving cGMP unaffected. Emiglitate, a selective inhibitor of a-glucoside hydrolase activities, was able to markedly inhibit the stimulatory effect of exogenous CO on both glucose-stimulated insulin secretion and the activity of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase, while no appreciable effect on the activities of other lysosomal enzyme activities measured was found. We propose that CO and NO, both produced in significant quantities in the islets of Langerhans, have interacting regulatory roles on glucose-stimulated insulin secretion. This regulation is, at least in part, transduced through the activity of cGMP and the lysosomal/vacuolar system and the associated acid alpha-glucoside hydrolases, but probably also through a direct effect on the cAMP system.