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首页> 外文期刊>Cell metabolism >Glucose-induced cyclic AMP oscillations regulate pulsatile insulin secretion.
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Glucose-induced cyclic AMP oscillations regulate pulsatile insulin secretion.

机译：葡萄糖引起的循环AMP振荡调节搏动性胰岛素分泌。

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摘要

Cyclic AMP (cAMP) and Ca(2+) are key regulators of exocytosis in many cells, including insulin-secreting beta cells. Glucose-stimulated insulin secretion from beta cells is pulsatile and involves oscillations of the cytoplasmic Ca(2+) concentration ([Ca(2+)](i)), but little is known about the detailed kinetics of cAMP signaling. Using evanescent-wave fluorescence imaging we found that glucose induces pronounced oscillations of cAMP in the submembrane space of single MIN6 cells and primary mouse beta cells. These oscillations were preceded and enhanced by elevations of [Ca(2+)](i). However, conditions raising cytoplasmic ATP could trigger cAMP elevations without accompanying [Ca(2+)](i) rise, indicating that adenylyl cyclase activity may be controlled also by the substrate concentration. The cAMP oscillations correlated with pulsatile insulin release. Whereas elevation of cAMP enhanced secretion, inhibition of adenylyl cyclases suppressed both cAMP oscillations and pulsatile insulin release. We conclude that cell metabolism directly controls cAMP and that glucose-induced cAMP oscillations regulate the magnitude and kinetics of insulin exocytosis.
机译：环状AMP（cAMP）和Ca（2+）是许多细胞（包括分泌胰岛素的β细胞）胞吐作用的关键调节剂。从β细胞的葡萄糖刺激的胰岛素分泌是搏动性的，并且涉及细胞质Ca（2+）浓度（[Ca（2 +）]（i））的振荡，但对cAMP信号传导的详细动力学知之甚少。使用e逝波荧光成像，我们发现葡萄糖在单个MIN6细胞和原代小鼠β细胞的亚膜空间诱导cAMP的明显振荡。这些振荡是由[Ca（2 +）]（i）升高引起的。但是，提高细胞质ATP的条件可能会触发cAMP升高而不会伴随[Ca（2 +）]（i）升高，表明腺苷酸环化酶活性也可能受底物浓度控制。 cAMP振荡与搏动性胰岛素释放相关。 cAMP的升高会增强分泌，而腺苷酸环化酶的抑制会抑制cAMP振荡和搏动性胰岛素释放。我们得出结论，细胞代谢直接控制cAMP，而葡萄糖诱导的cAMP振荡调节胰岛素胞吐作用的大小和动力学。

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