Ohta M, Nelson D, Nelson J, Meglasson M D, Erecińska M
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104-6084.
J Biol Chem. 1990 Oct 15;265(29):17525-32.
The effects of lowered O2 tension on insulin secretion and changes in cellular energy parameters were investigated in isolated rat pancreatic islets perifused with buffers equilibrated with 21, 9, 5, and 1% oxygen and containing 5 mM glucose. Decreasing the external [O2] reduced the amount of insulin released in response to 16 mM glucose, 20 mM alpha-ketoisocaproic acid, and 40 mM KCl. Secretion elicited by high glucose or KCl had declined significantly at 9% oxygen, whereas that caused by alpha-ketoisocaproic acid became inhibited below 5% O2. Lowering the oxygen tension also decreased the ability of islets to respond with a rise in [ATP]/[ADP] upon stimulation with metabolic secretagogues. This reduction in the evoked increase in the nucleotide ratios paralleled the inhibition of stimulated insulin secretion. Addition of 2 mM amytal markedly decreased the islet energy level and eliminated the secretory response to 16 mM glucose. The results suggest that enhancement of B-cell energy production and a consequent rise in [ATP] (or [ATP]/[ADP]) are a necessary event for the hormone release elicited by high glucose and alpha-ketoisocaproic acid. A decrease in temperature inhibited insulin secretion with all three secretagogues tested. The energies of activation were similar for high glucose and KCl-induced secretion, about 20 kcal/mol, but were higher for alpha-ketoisocaproic acid, about 35 kcal/mol. At 28 degrees C, the [ATP]/[ADP] was larger than that at 38 degrees C (8 versus 5) and was not increased further upon addition of 16 mM glucose. It is suggested that a decrease in the rate of energy production at lowered temperatures may contribute to the inhibition of insulin release caused by metabolic secretagogues.
在分离的大鼠胰岛中，研究了降低氧张力对胰岛素分泌及细胞能量参数变化的影响。胰岛用与含5 mM葡萄糖且分别平衡于21%、9%、5%和1%氧气的缓冲液进行灌流。降低外部[O₂]会减少胰岛对16 mM葡萄糖、20 mMα-酮异己酸和40 mM KCl的胰岛素释放量。在9%氧气时，高糖或KCl引发的分泌已显著下降，而α-酮异己酸引发的分泌在低于5% O₂时受到抑制。降低氧张力还会降低胰岛在代谢性促分泌剂刺激下使[ATP]/[ADP]升高的反应能力。这种核苷酸比率诱发增加的降低与刺激的胰岛素分泌受到抑制平行。添加2 mM阿米妥显著降低胰岛能量水平，并消除对16 mM葡萄糖的分泌反应。结果表明，增强B细胞能量产生以及随之而来的[ATP]（或[ATP]/[ADP]）升高是高糖和α-酮异己酸引发激素释放的必要事件。降低温度会抑制所测试的所有三种促分泌剂的胰岛素分泌。高糖和KCl诱导分泌的活化能相似，约为20 kcal/mol，但α-酮异己酸的活化能更高，约为35 kcal/mol。在28℃时，[ATP]/[ADP]比38℃时更大（8比5），并且在添加16 mM葡萄糖后不会进一步升高。提示在较低温度下能量产生速率降低可能是代谢性促分泌剂导致胰岛素释放受抑制的原因。
