Streptozotocin, an O-GlcNAcase inhibitor, blunts insulin and growth hormone secretion.
Streptozotocin, an O-GlcNAcase inhibitor, blunts insulin and growth hormone secretion.
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链脲佐菌素是一种 O-GlcNAcase 抑制剂，可抑制胰岛素和生长激素的分泌。
DOI：
10.1016/s0303-7207(02)00155-7
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发表时间：
2002
影响因子：
4.1
通讯作者：
Kudlow,JeffreyE
中科院分区：
文献类型：
--
作者：
Liu,Kan;Paterson,AndrewJ;Konrad,RobertJ;Parlow,AF;Jimi,Shiro;Roh,Meejeon;ChinJr,Edward;Kudlow,JeffreyE
2型糖尿病是由营养过剩和多个基因之间复杂的相互作用引起的。尽管胰腺β细胞通常通过快速胰岛素释放（第一时相胰岛素分泌）对葡萄糖激发作出反应，但几乎所有具有显著空腹高血糖症的2型糖尿病患者都丧失了这种急性反应。我们以前的研究表明，葡萄糖代谢产物，蛋白质O-连接的N-乙酰葡萄糖胺修饰（O-GlcNAc）的不可逆细胞内积累与胰腺β细胞凋亡相关。在本研究中，我们表明，链脲佐菌素（STZ），非竞争性化学阻断剂的O-GlcNAc酶，诱导胰岛素分泌缺陷在离体大鼠胰岛细胞。相比之下，β细胞中葡萄糖至葡糖胺代谢下调的转基因小鼠表现出增强的胰岛素分泌能力。有趣的是，O-GlcNAcase活性的STZ阻断也与生长激素分泌缺陷和细胞内分泌囊泡运输受损相关。这些结果为O-GlcNAc在胰岛素分泌中的作用以及O-GlcNAc可能参与一般葡萄糖调节的激素分泌途径提供了证据。
Type 2 diabetes mellitus results from a complex interaction between nutritional excess and multiple genes. Whereas pancreatic β-cells normally respond to glucose challenge by rapid insulin release (first phase insulin secretion), there is a loss of this acute response in virtually all of the type 2 diabetes patients with significant fasting hyperglycemia. Our previous studies demonstrated that irreversible intracellular accumulation of a glucose metabolite, protein O-linked N-acetylglucosamine modification (O-GlcNAc), is associated with pancreatic β-cell apoptosis. In the present study, we show that streptozotocin (STZ), a non-competitive chemical blocker of O-GlcNAcase, induces an insulin secretory defect in isolated rat islet cells. In contrast, transgenic mice with down-regulated glucose to glucosamine metabolism in β-cells exhibited an enhanced insulin secretion capacity. Interestingly, the STZ blockade of O-GlcNAcase activity is also associated with a growth hormone secretory defect and impairment of intracellular secretory vesicle trafficking. These results provide evidence for the roles of O-GlcNAc in the insulin secretion and possible involvement of O-GlcNAc in general glucose-regulated hormone secretion pathways.