Green I C, Delaney C A, Cunningham J M, Karmiris V, Southern C
Biochemistry Laboratory, School of Biological Sciences University of Sussex, Brighton, UK.
Diabetologia. 1993 Jan;36(1):9-16. doi: 10.1007/BF00399087.
When islets were cultured with interleukin-1 beta (1 or 100 pmol/l) for 12 h in arginine-containing medium, cyclic GMP levels were increased 1.6- and 4.5-fold respectively. The arginine analogue, N-omega-nitro-L-arginine methyl ester, which blocks nitric oxide formation and partially reverses inhibition of insulin secretion by 100 pmol/l interleukin-1 beta, largely, but not completely, blocked generation of cyclic GMP. Treatment of islets with 100 pmol/l interleukin-1 beta for 12 h significantly decreased islet cyclic AMP generation in the absence of isobutylmethylxanthine (from 13.1 +/- 0.7 to 9.3 +/- 0.8 fmol/micrograms islet protein), this fall was arginine-dependent and may have resulted from an effect on a cyclic AMP phosphodiesterase, since it was masked if isobutylmethylxanthine was present. Isobutylmethylxanthine (0.4 mmol/l) reduced the inhibitory potency of interleukin-1 beta in 15 h slightly but significantly from 80.5 to 59.0%. The morpholinosydnonimine SIN-1, which is a nitric oxide donor, inhibited insulin secretion, raised islet cyclic GMP and lowered cyclic AMP; its effects were similar to those of interleukin-1 beta. However, 6-anilinoquinoline-5,8-quinone, [LY83583 (1-10 mumol/l)], inhibited insulin secretion, and significantly decreased cyclic GMP while 8-bromocyclic GMP stimulated insulin secretion. Both low- and high-dose interleukin-1 beta treatment give a large arginine-dependent and a small, yet significant, arginine-independent increase in cyclic GMP. The inhibitory effect of SIN-1 or interleukin-1 beta on insulin secretion seems to depend to a small extent on decreased islet cyclic AMP, though sustained increases in nitric oxide or depleted islet GTP may directly affect the secretory process.
当胰岛在含精氨酸的培养基中与白细胞介素 -1β（1或100 pmol/L）一起培养12小时时，环鸟苷酸（cGMP）水平分别升高了1.6倍和4.5倍。精氨酸类似物N -ω-硝基 -L -精氨酸甲酯可阻断一氧化氮的形成，并部分逆转100 pmol/L白细胞介素 -1β对胰岛素分泌的抑制作用，它在很大程度上但并非完全阻断了环鸟苷酸的生成。用100 pmol/L白细胞介素 -1β处理胰岛12小时，在不存在异丁基甲基黄嘌呤的情况下，显著降低了胰岛环磷酸腺苷（cAMP）的生成（从13.1±0.7降至9.3±0.8 fmol/μg胰岛蛋白），这种下降依赖于精氨酸，可能是由于对环磷酸腺苷磷酸二酯酶的作用，因为如果存在异丁基甲基黄嘌呤，这种下降就会被掩盖。异丁基甲基黄嘌呤（0.4 mmol/L）在15小时内使白细胞介素 -1β的抑制效力略有但显著地从80.5%降至59.0%。吗啉代 sydnonimine SIN -1是一种一氧化氮供体，它抑制胰岛素分泌，提高胰岛环鸟苷酸水平并降低环磷酸腺苷水平；其作用与白细胞介素 -1β相似。然而，6 -苯胺基喹啉 -5,8 -醌，[LY83583（1 - 10 μmol/L）]，抑制胰岛素分泌，并显著降低环鸟苷酸水平，而8 -溴环鸟苷酸刺激胰岛素分泌。低剂量和高剂量白细胞介素 -1β处理均使环鸟苷酸产生大量的精氨酸依赖性增加以及少量但显著的精氨酸非依赖性增加。SIN -1或白细胞介素 -1β对胰岛素分泌的抑制作用似乎在一定程度上依赖于胰岛环磷酸腺苷的减少，尽管一氧化氮的持续增加或胰岛鸟苷三磷酸（GTP）的消耗可能直接影响分泌过程。
