Zawalich W S, Zawalich K C
Yale University School of Nursing, 100 Church Street South, New Haven, Connecticut 06536-0740, USA.
J Endocrinol. 2000 Jul;166(1):111-20. doi: 10.1677/joe.0.1660111.
Islets from fed and 24-h-fasted rats were studied immediately after collagenase isolation. (1) After a 24-h fast, the insulin secretory responses to 8 mM glucose measured during perifusion were reduced by more than 90% from islets of fasted donors. (2) Increasing glucose to 11 or 27.5 mM resulted in enhanced insulin secretion from islets of fasted animals. (3) Fasting did not reduce islet insulin content. (4) Responses to 8 or 27.5 mM glucose were not affected if fatty acid-free albumin was used during the perifusion. (5) Inclusion of alpha-ketoisocaproate (5 mM), monomethyl succinate (10 mM) or carbachol (10 microM) significantly amplified insulin release from fasted islets in the simultaneous presence of 8 mM glucose. (6) Phospholipase C activation by glucose, carbachol or their combination was not adversely affected by fasting. (7) The response to the protein kinase C activator, phorbol 12-myristate 13-acetate (500 nM), was reduced by about 60% after fasting. (8) Extending the fast to 48 h resulted in a severe decline in response to 11 mM glucose; however, the further addition of 10 microM carbachol still enhanced release from these islets. The results confirm that caloric restriction impairs islet sensitivity to glucose stimulation and that protein kinase C may be involved in the reduction of glucose-induced insulin release from these islets. The activation of phospholipase C by cholinergic stimulation may contribute to the maintenance of insulin secretion from calorically restricted animals. These results also demonstrate that free fatty acids are not essential for glucose to evoke secretion from isolated islets of fasted donors.
对用胶原酶分离后立即取自喂食和禁食24小时大鼠的胰岛进行了研究。(1) 禁食24小时后，在灌流期间测得的对8 mM葡萄糖的胰岛素分泌反应比禁食供体的胰岛降低了90%以上。(2) 将葡萄糖浓度提高到11或27.5 mM可增强禁食动物胰岛的胰岛素分泌。(3) 禁食并未降低胰岛胰岛素含量。(4) 如果在灌流期间使用无脂肪酸白蛋白，则对8或27.5 mM葡萄糖的反应不受影响。(5) 在同时存在8 mM葡萄糖的情况下，加入α-酮异己酸（5 mM）、单甲基琥珀酸（10 mM）或卡巴胆碱（10 μM）可显著增强禁食胰岛的胰岛素释放。(6) 葡萄糖、卡巴胆碱或它们的组合对磷脂酶C的激活不受禁食的不利影响。(7) 禁食后对蛋白激酶C激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯（500 nM）的反应降低了约60%。(8) 将禁食时间延长至48小时导致对11 mM葡萄糖的反应严重下降；然而，进一步加入10 μM卡巴胆碱仍可增强这些胰岛的释放。结果证实，热量限制会损害胰岛对葡萄糖刺激的敏感性，蛋白激酶C可能参与了这些胰岛中葡萄糖诱导的胰岛素释放的减少。胆碱能刺激对磷脂酶C的激活可能有助于维持热量限制动物的胰岛素分泌。这些结果还表明，游离脂肪酸对于葡萄糖从禁食供体的分离胰岛中诱发分泌并非必不可少。
