MacDonald M J, Fahien L A, McKenzie D I, Moran S M
Department of Pediatrics, University of Wisconsin Medical School, Madison 53706.
Am J Physiol. 1990 Oct;259(4 Pt 1):E548-54. doi: 10.1152/ajpendo.1990.259.4.E548.
Agents that stimulate insulin release from fresh pancreatic islets were tested for their ability to capacitate pancreatic islets to secrete insulin and to support beta-cell survival in tissue culture. Capacitation was defined as the ability to release insulin after 24 h in culture in the presence of an insulinotropic concentration of a secretagogue. Viable islets that lose glucose-induced insulin release gradually regain it during culture for 24 h in 20 mM glucose. Survival was defined as the ability to regain glucose-induced insulin release. To measure insulin release after culture, islets were incubated with various secretagogues in Krebs-Ringer buffer for 1 h. Examples of the diverse patterns of responses included the following. Glucose was the only secretagogue that capacitated glucose-induced release. Leucine-, leucine plus glutamine-, and glyceraldehyde-induced release remained capacitated after culture with no secretagogue. Culture at high glucose completely inhibited leucine-induced release. Culture at low glucose (1 mM) or at both high leucine and glutamine abolished glucose-induced release. Only leucine and glutamine capacitated monomethyl succinate-induced release. All agents including subinsulinotropic glucose (1 mM), except D-glyceraldehyde, permitted islet survival. Thus the metabolic pathways for initiation, capacitation, and survival are not identical between and within secretagogues. There is a reciprocal relationship between leucine and glucose with respect to capacitation. Capacitation follows a time course, which suggests that it is regulated by enzyme induction.
对能刺激新鲜胰岛释放胰岛素的药物进行了测试，以评估它们使胰岛在组织培养中分泌胰岛素并支持β细胞存活的能力。获能被定义为在促胰岛素分泌剂达到促胰岛素浓度的情况下，培养24小时后释放胰岛素的能力。在20 mM葡萄糖中培养24小时期间，逐渐失去葡萄糖诱导胰岛素释放能力的活胰岛会逐渐恢复该能力。存活被定义为恢复葡萄糖诱导胰岛素释放的能力。为了测量培养后的胰岛素释放，将胰岛在Krebs-Ringer缓冲液中与各种促分泌剂孵育1小时。不同反应模式的示例如下。葡萄糖是唯一能使葡萄糖诱导释放获能的促分泌剂。在不添加促分泌剂的情况下培养后，亮氨酸、亮氨酸加谷氨酰胺和甘油醛诱导的释放仍具有获能能力。在高葡萄糖浓度下培养完全抑制了亮氨酸诱导的释放。在低葡萄糖（1 mM）浓度下或同时在高浓度亮氨酸和谷氨酰胺条件下培养会消除葡萄糖诱导的释放。只有亮氨酸和谷氨酰胺能使单甲基琥珀酸诱导的释放获能。除D-甘油醛外，包括亚促胰岛素浓度葡萄糖（1 mM）在内的所有药物都能使胰岛存活。因此，不同促分泌剂之间以及同一促分泌剂内部，引发、获能和存活的代谢途径并不相同。在获能方面，亮氨酸和葡萄糖之间存在相互关系。获能遵循一定的时间进程，这表明它受酶诱导的调控。
