The Role of PDE3B Phosphorylation in the Inhibition of Lipolysis by Insulin
The Role of PDE3B Phosphorylation in the Inhibition of Lipolysis by Insulin
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DOI：
10.1128/mcb.00422-15
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发表时间：
2015-08-01
影响因子：
5.3
通讯作者：
Birnbaum, Morris J.
中科院分区：
文献类型：
--
作者：
DiPilato, Lisa M.;Ahmad, Faiyaz;Birnbaum, Morris J.
胰岛素对脂肪细胞脂解的抑制对于全身能量稳态是重要的;它的破坏被认为有助于胰岛素抵抗和2型糖尿病的发展。胰岛素抗脂解作用的主要靶点被认为是磷酸二酯酶3B（PDE 3B），其被Akt磷酸化导致脂解第二信使环AMP（cAMP）的加速降解。为了从遗传学上检验这一假设，检测了缺乏PDE 3B的棕色脂肪细胞对脂解的调节。在Pde 3b敲除（KO）脂肪细胞中，胰岛素不能抑制β-肾上腺素能受体刺激的甘油释放。在KO脂肪细胞中重新表达野生型PDE 3B完全挽救了胰岛素对脂解的作用。令人惊讶的是，消除主要Akt磷酸化位点的PDE 3B突变形式，鼠S273，也恢复了胰岛素抑制脂解的能力。总之，这些数据表明，磷酸化的PDE 3B的Akt是不需要胰岛素抑制脂肪细胞脂解。
Inhibition of adipocyte lipolysis by insulin is important for whole-body energy homeostasis; its disruption has been implicated as contributing to the development of insulin resistance and type 2 diabetes mellitus. The main target of the antilipolytic action of insulin is believed to be phosphodiesterase 3B (PDE3B), whose phosphorylation by Akt leads to accelerated degradation of the prolipolytic second messenger cyclic AMP (cAMP). To test this hypothesis genetically, brown adipocytes lacking PDE3B were examined for their regulation of lipolysis. In Pde3b knockout (KO) adipocytes, insulin was unable to suppress beta-adrenergic receptor-stimulated glycerol release. Reexpressing wild-type PDE3B in KO adipocytes fully rescued the action of insulin against lipolysis. Surprisingly, a mutant form of PDE3B that ablates the major Akt phosphorylation site, murine S273, also restored the ability of insulin to suppress lipolysis. Taken together, these data suggest that phosphorylation of PDE3B by Akt is not required for insulin to suppress adipocyte lipolysis.