While searching for a counterpart to cyclic AMP, a new compound was found to inhibit adenylate cyclase. It was identified as prostaglandyl‐(15‐4′)‐myo‐inositol (1′:2′‐cyclic)‐phosphate (cyclic PIP). The substrates for its biosynthesis are prostaglandin E (PGE) and the novel inositol phosphate, guanosine diphospho‐4‐myo‐inositol 1:2‐cyclic phosphate (n‐IP). The basic regulatory properties of cyclic PIP are to inhibit dose‐dependently protein kinase A (PKA) and to seven‐fold activate protein ser/thr phosphatase holoenzyme. These regulations occur as rapidly as the activation of PKA by cyclic AMP. Such regulatory properties are essential for the meticulous regulation of the equilibrium between the phospho‐ and de‐phospho‐form of interconvertible enzymes. The synthesis of cyclic PIP is stimulated by insulin and noradrenaline (α‐receptor action). The insulin‐stimulated cyclic PIP synthase is active in a tyrosine‐phosphorylated state. A comparable characterization of the adrenaline‐stimulated cyclic PIP synthase is still incomplete. In streptozotocin‐diabetic rats, the hormonal stimulation of cyclic PIP synthesis decreases with time. Cyclic PIP synthesis is activated by biguanides as metformin two to four‐fold and by antihypertensive drugs two‐fold. Inhibition of cyclic PIP synthesis leads to a metabolic state as observed in early‐stage type‐2 diabetes. In summary, all living cells synthesize cyclic PIP, which switches on anabolism, whereas cyclic AMP triggers catabolism.

中文翻译：

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Prostaglandylinositol 环状磷酸酯，环状 AMP 的天然拮抗剂

在寻找环状 AMP 的对应物时，发现了一种新化合物可以抑制腺苷酸环化酶。它被鉴定为前列腺素-(15-4')-肌醇(1':2'-环状)-磷酸(环状PIP)。其生物合成的底物是前列腺素 E (PGE) 和新型肌醇磷酸酯，鸟苷二磷酸-4-肌醇 1:2-环磷酸酯 (n-IP)。环状 PIP 的基本调节特性是剂量依赖性地抑制蛋白激酶 A (PKA) 和七倍激活蛋白丝氨酸/苏氨酸磷酸酶全酶。这些调节与环 AMP 对 PKA 的激活一样迅速。这种调节特性对于精细调节可相互转化酶的磷酸化和去磷酸化形式之间的平衡至关重要。胰岛素和去甲肾上腺素（α-受体作用）会刺激环状 PIP 的合成。胰岛素刺激的环状 PIP 合酶在酪氨酸磷酸化状态下具有活性。肾上腺素刺激的环状 PIP 合酶的类似特征仍然不完整。在链脲佐菌素糖尿病大鼠中，循环 PIP 合成的激素刺激随时间降低。环状 PIP 合成被双胍激活二至四倍和抗高血压药物的两倍。在早期 2 型糖尿病中观察到的循环 PIP 合成的抑制导致代谢状态。总之，所有活细胞都会合成循环 PIP，它开启合成代谢，而循环 AMP 触发分解代谢。循环 PIP 合成的激素刺激随时间降低。环状 PIP 合成被双胍激活二至四倍和抗高血压药物的两倍。在早期 2 型糖尿病中观察到的循环 PIP 合成的抑制导致代谢状态。总之，所有活细胞都会合成循环 PIP，它开启合成代谢，而循环 AMP 触发分解代谢。循环 PIP 合成的激素刺激随时间降低。环状 PIP 合成被双胍激活二至四倍和抗高血压药物的两倍。在早期 2 型糖尿病中观察到的循环 PIP 合成的抑制导致代谢状态。总之，所有活细胞都会合成循环 PIP，它开启合成代谢，而循环 AMP 触发分解代谢。