Pareja A, Tinahones F J, Soriguer F J, Monzón A, Esteva de Antonio I, García-Arnes J, Olveira G, Ruiz de Adana M S
Metabolic Unit, Endocrinology Section, Carlos Haya Regional Hospital, Malaga, Spain.
Diabetes Res Clin Pract. 1997 Dec;38(3):143-9. doi: 10.1016/s0168-8227(97)00103-4.
The aim of the present study is to examine the influence which different concentrations of free fatty acids (FFAs) have on the insulin secretion response of the islets of Langerhans when the culture is prolonged over a week. Animals were killed by decapitation and pancreatic islets of Langerhans isolated. The islets were incubated in enriched RPMI and oleic or linoleic acid was added at concentrations of 0.04, 0.1, 0.375, and 1 mmol/l. The medium without FFAs was used as a control. The culture time was 7 days. For insulin secretion studies, islets were selected after preincubation in batches of six islets in 1 ml of KRB (Krebs-Ringer buffer) containing one of the following: 5.5, 11.1, 16 or 26.7 mmol/l glucose, 10 mumol/l forskolin or 20 mmol/l arginine. The results showed a significant increase in insulin secretion observed after culture with 1 mmol/l oleic and linoleic acid compared to the other concentrations and the control culture for all the secretagogues used. However, at this same concentrations no increase was observed in insulin secretion as the glucose concentration rose, and this was noticeable with linoleic acid at concentrations of 0.375 mmol/l. In conclusion, culture of islets of Langerhans for a week with high concentrations of unsaturated fatty acids produces a hypersecretion of insulin which is not influenced by secretagogues such as glucose, arginine, or forskolin. The loss of gluco-sensitivity may become greater as the degree of unsaturation of the fatty acid used increases.
本研究的目的是考察当培养时间延长至一周以上时，不同浓度的游离脂肪酸（FFA）对胰岛胰岛素分泌反应的影响。通过断头法处死动物并分离胰岛。将胰岛置于富集的RPMI培养基中，并添加浓度为0.04、0.1、0.375和1 mmol/l的油酸或亚油酸。不含FFA的培养基用作对照。培养时间为7天。对于胰岛素分泌研究，将胰岛在含有以下物质之一的1 ml KRB（ Krebs-Ringer缓冲液）中预孵育后进行选择：5.5、11.1、16或26.7 mmol/l葡萄糖、10 μmol/l福斯高林或20 mmol/l精氨酸。结果显示，与其他浓度以及对照培养相比，在使用所有促分泌剂的情况下，用1 mmol/l油酸和亚油酸培养后观察到胰岛素分泌显著增加。然而，在相同浓度下，随着葡萄糖浓度升高未观察到胰岛素分泌增加，在0.375 mmol/l亚油酸浓度下这种情况尤为明显。总之，用高浓度不饱和脂肪酸培养胰岛一周会产生胰岛素分泌过多的情况，且不受葡萄糖、精氨酸或福斯高林等促分泌剂的影响。随着所用脂肪酸不饱和度的增加，葡萄糖敏感性的丧失可能会更大。
