Green I C, Tadayyon M
Biochemistry Dept., University of Sussex, Brighton, England.
Life Sci. 1988;42(21):2123-30. doi: 10.1016/0024-3205(88)90126-9.
The inadequate insulin secretory response to glucose stimulation in non-insulin dependent diabetes has been attributed to many factors including high PGE2 levels blunting the secretory response, and to the existence of inhibitory opiate activity in vivo. The purpose of the present work was to see if there was a connection between these two independent theories. Radioimmunoassayable PGE2 in islets of Langerhans was found to be proportional to islet number and protein content and was typically 4 to 5pg/micrograms islet protein. Indomethacin (2.8 X 10(-5) M), sodium salicylate (1.25 X 10(-3) M) and chlorpropamide (7.2 X 10(-5) M) all lowered islet PGE2 levels and stimulated insulin release in vitro. Dynorphin (1-13), stimulated insulin release at a concentration of 6 X 10(-9) M, while lowering islet PGE2. Conversely, at a higher concentration, (6 X 10(-7) M), dynorphin had no stimulatory effect on insulin secretion and did not lower PGE2 levels in islets or in the incubation media. The stimulatory effects of dynorphin and sodium salicylate on insulin secretion were blocked by exogenous PGE2 (10(-5) M). PGE2 at a lower concentration (10(-9) M) did not exert any inhibitory effect on dynorphin- or sodium salicylate-induced insulin release. This concentration of exogenous PGE2 stimulated insulin release in the presence of 6mM glucose. Results from these experiments suggest that since an opioid peptide can lower endogenous PGE2 production in islets and since the stimulatory effects of the opioid peptide are reversed by exogenous PGE2 there may be interactions between these two modulators of insulin secretion.
非胰岛素依赖型糖尿病患者对葡萄糖刺激的胰岛素分泌反应不足，这归因于多种因素，包括高水平的前列腺素E2（PGE2）削弱了分泌反应，以及体内存在抑制性阿片样物质活性。本研究的目的是探讨这两种独立理论之间是否存在联系。发现胰岛中可通过放射免疫测定的PGE2与胰岛数量和蛋白质含量成正比，通常为每微克胰岛蛋白4至5皮克。吲哚美辛（2.8×10⁻⁵M）、水杨酸钠（1.25×10⁻³M）和氯磺丙脲（7.2×10⁻⁵M）均降低了胰岛PGE2水平，并在体外刺激胰岛素释放。强啡肽（1 - 13）在浓度为6×10⁻⁹M时刺激胰岛素释放，同时降低胰岛PGE2水平。相反，在较高浓度（6×10⁻⁷M）时，强啡肽对胰岛素分泌没有刺激作用，也没有降低胰岛或孵育培养基中的PGE2水平。强啡肽和水杨酸钠对胰岛素分泌的刺激作用被外源性PGE2（10⁻⁵M）阻断。较低浓度（10⁻⁹M）的PGE2对强啡肽或水杨酸钠诱导的胰岛素释放没有任何抑制作用。这种浓度的外源性PGE2在存在6mM葡萄糖的情况下刺激胰岛素释放。这些实验结果表明，由于一种阿片肽可以降低胰岛内源性PGE2的产生，并且由于阿片肽的刺激作用被外源性PGE2逆转，这两种胰岛素分泌调节因子之间可能存在相互作用。
