Cell子刊:敲除脂肪组织中的PKCɛ,提升小鼠的糖耐受
创作:Kang 审核:szx 2018年10月25日
  • 全身敲除PKCε在小鼠中对高脂饮食诱导的葡萄糖不耐受及胰岛素抵抗起保护作用,但未检测到胰岛素受体被PKCε磷酸化;
  • 肝脏特异性敲除PKCε无上述保护作用;
  • 而脂肪组织特异性敲除PKCε的小鼠表现出糖耐量的提高,但未检测到PKCɛ依赖性的胰岛素信号通路活化;
  • 脂肪组织中的PKCɛ的缺失可改变细胞连接及核内体相关蛋白的磷酸化,进一步影响肝脏中糖稳态及脂质代谢相关基因的表达;
  • PKCε通过脂肪组织-肝脏之间的互作以调节糖稳态。
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szx
过去的研究认为,肝脏中的PKCε可通过磷酸化胰岛素受体以抑制胰岛素的作用。然而在Cell Metabolism上发表的一项最新研究中发现,在糖耐受中起重要调节作用的,是脂肪组织中,而非肝脏中的PKCε。脂肪组织中的PKCε通过调节肝脏中的相关基因表达,以调节小鼠体内的糖稳态。
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Cell Metabolism [IF:21.567]

Protein Kinase C Epsilon Deletion in Adipose Tissue, but Not in Liver, Improves Glucose Tolerance

脂肪组织特异性(而非肝脏)的敲除蛋白激酶Cɛ能提高糖耐量

10.1016/j.cmet.2018.09.013

2018-10-08, Article

Abstract & Authors:展开

Abstract:收起
Protein kinase C epsilon (PKCɛ) activation in the liver is proposed to inhibit insulin action through phosphorylation of the insulin receptor. Here, however, we demonstrated that global, but not liver-specific, deletion of PKCɛ in mice protected against diet-induced glucose intolerance and insulin resistance. Furthermore, PKCɛ-dependent alterations in insulin receptor phosphorylation were not detected. Adipose-tissue-specific knockout mice did exhibit improved glucose tolerance, but phosphoproteomics revealed no PKCɛ-dependent effect on the activation of insulin signaling pathways. Altered phosphorylation of adipocyte proteins associated with cell junctions and endosomes was associated with changes in hepatic expression of several genes linked to glucose homeostasis and lipid metabolism. The primary effect of PKCɛ on glucose homeostasis is, therefore, not exerted directly in the liver as currently posited, and PKCɛ activation in this tissue should be interpreted with caution. However, PKCɛ activity in adipose tissue modulates glucose tolerance and is involved in crosstalk with the liver.

First Authors:
Amanda E Brandon,Bing M Liao,Barbara Diakanastasis

Correspondence Authors:
Carsten Schmitz-Peiffer

All Authors:
Amanda E Brandon,Bing M Liao,Barbara Diakanastasis,Benjamin L Parker,Katy Raddatz,Sophie A McManus,Liam O'Reilly,Erica Kimber,A Gabrielle van der Kraan,Dale Hancock,Darren C Henstridge,Peter J Meikle,Gregory J Cooney,David E James,Saskia Reibe,Mark A Febbraio,Trevor J Biden,Carsten Schmitz-Peiffer

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