Zawalich W S, Zawalich K C
Yale University School of Nursing, New Haven, Connecticut 06536-0740, USA.
Am J Physiol. 1997 Apr;272(4 Pt 1):E671-7. doi: 10.1152/ajpendo.1997.272.4.E671.
Groups of rat or mouse islets were isolated and perifused with 20 mM glucose plus 200 microM diazoxide. The further addition of 30 mM K+ resulted in a rapid and sustained biphasic insulin secretory response. The onset of secretion in response to the addition of K+ was comparable in both species, but the magnitude of the response was significantly greater from rat islets. After the labeling of islet phosphoinositide pools with 2-[3H]inositol, the accumulation of labeled inositol phosphates (IP) in response to 30 mM K+ addition in the simultaneous presence of 20 mM glucose plus diazoxide was assessed. The addition of 30 mM K+ significantly increased IP accumulation approximately 300% in rat islets, whereas only an insignificant 25-30% increase was observed in mouse islets. The protein kinase C inhibitor staurosporine (50 nM) dramatically reduced the sustained secretory response from rat islets in the presence of 30 mM K+, 20 mM glucose, and diazoxide. Its effect was minimal on mouse islets and a significant inhibitory effect on insulin secretion was observed only during the final 5 min of the perifusion. The further addition of carbachol, an agonist that activates an isozyme of phospholipase C distinct from that activated by glucose, together with K+, 20 mM glucose, plus diazoxide resulted in a sustained amplification of insulin secretion from mouse but not rat islets. K+ (30 mM)-induced insulin secretion in the presence of 3 mM glucose was similar from perifused rat or mouse islets, a finding that would seem to preclude the activation of voltage-regulated Ca2+ channels as the pertinent difference. These results confirm previous observations with these species and document another anomaly that exists between the responses of rat islets compared with mouse islets. The inability to activate a nutrient- and calcium-regulated phospholipase C isozyme in mouse islets to the same extent as in rat islets appears to account, at least in part, for these different insulin secretory responses under these unique conditions.
分离出大鼠或小鼠胰岛群，并用含20 mM葡萄糖加200 μM二氮嗪的溶液进行灌流。进一步添加30 mM K⁺会导致快速且持续的双相胰岛素分泌反应。两种物种对添加K⁺的分泌起始情况相当，但大鼠胰岛的反应幅度明显更大。在用2-[³H]肌醇标记胰岛磷酸肌醇池后，评估在同时存在20 mM葡萄糖加二氮嗪的情况下，添加30 mM K⁺后标记肌醇磷酸（IP）的积累情况。添加30 mM K⁺可使大鼠胰岛中的IP积累显著增加约300%，而在小鼠胰岛中仅观察到微不足道的25 - 30%的增加。蛋白激酶C抑制剂星形孢菌素（50 nM）在存在30 mM K⁺、20 mM葡萄糖和二氮嗪的情况下，显著降低了大鼠胰岛的持续分泌反应。其对小鼠胰岛的作用极小，仅在灌流的最后5分钟观察到对胰岛素分泌有显著抑制作用。进一步添加卡巴胆碱（一种激活与葡萄糖激活的磷脂酶C同工酶不同的激动剂），与K⁺、20 mM葡萄糖加二氮嗪一起，导致小鼠而非大鼠胰岛的胰岛素分泌持续放大。在存在3 mM葡萄糖的情况下，灌流的大鼠或小鼠胰岛对K⁺（30 mM）诱导的胰岛素分泌相似，这一发现似乎排除了电压调节性Ca²⁺通道的激活作为相关差异。这些结果证实了之前对这些物种的观察，并记录了大鼠胰岛与小鼠胰岛反应之间存在的另一个异常情况。在这些独特条件下，小鼠胰岛无法像大鼠胰岛那样程度地激活营养物和钙调节的磷脂酶C同工酶，这似乎至少部分解释了这些不同的胰岛素分泌反应。
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