Dominance of cyclooxygenase-2 in the regulation of pancreatic islet prostaglandin synthesis
Dominance of cyclooxygenase-2 in the regulation of pancreatic islet prostaglandin synthesis
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DOI：
10.2337/diabetes.47.9.1379
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发表时间：
1998-09-01
期刊：
影响因子：
7.7
通讯作者：
Robertson, RP
中科院分区：
文献类型：
--
作者：
Robertson, RP
在过去的十年里，前列腺素（PG）的药理学和生理学有了重大的科学发现。这些发现中最主要的是鉴定了两种不同形式的环加氧酶（COX），一种是组成型的，一种是诱导型的，这两种形式都存在于大多数组织中。胰岛是这个规则的一个例外，因为它持续和主要表达诱导形式COX-2。研究还发现，非甾体类抗炎药对两种形式的COX具有不同的效力，这一发现具有深远的临床意义。一个同样重要的发现是PGE(2)，已知它可以负向调节葡萄糖诱导的胰岛素分泌，至少有四种不同的受体亚型，具有不同的作用机制和代谢后果。我们对PG合成分子调控的理解的这些最新变化要求我们重新考虑先前的假设，这些假设涉及PGE(2)在生理和病理生理状态下作为β细胞功能的调节剂。
Dramatic, scientifically important discoveries in prostaglandin (PG) pharmacology and physiology have taken place over the past decade. Chief among these discoveries is the identification of two separate forms of cyclooxygenase (COX), a constitutive and an inducible form, both of which exist in most tissues. The pancreatic islet is an exception to this rule because it continually and dominantly expresses the inducible form, COX-2. It has also been learned that nonsteroidal antiinflammatory drugs affect the two forms of COX with different potencies, a finding with far-reaching clinical implications. An equally important finding is that PGE(2), which is known to negatively modulate glucose-induced insulin secretion, has at least four different subtypes of receptors with different mechanisms of action and metabolic consequences. These recent changes in our understanding of the molecular regulation of PG synthesis call for a reconsideration of previous hypotheses involving PGE(2) as a regulator of beta-cell function in physiological and pathophysiological states.