PI4KIIα regulates insulin secretion and glucose homeostasis via a PKD-dependent pathway

Lunfeng Zhang; Jiangmei Li; Panpan Zhang; Zhen Gao; Yingying Zhao; Xinhua Qiao; Chang Chen

doi:10.1007/s41048-018-0049-z

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Lunfeng Zhang, Jiangmei Li, Panpan Zhang, Zhen Gao, Yingying Zhao, Xinhua Qiao, Chang Chen. PI4KIIα regulates insulin secretion and glucose homeostasis via a PKD-dependent pathway. Biophysics Reports, 2018, 4(1): 25-38. doi: 10.1007/s41048-018-0049-z

Citation:

Lunfeng Zhang, Jiangmei Li, Panpan Zhang, Zhen Gao, Yingying Zhao, Xinhua Qiao, Chang Chen. PI4KIIα regulates insulin secretion and glucose homeostasis via a PKD-dependent pathway. Biophysics Reports, 2018, 4(1): 25-38. doi: 10.1007/s41048-018-0049-z

Citation:

Lunfeng Zhang, Jiangmei Li, Panpan Zhang, Zhen Gao, Yingying Zhao, Xinhua Qiao, Chang Chen. PI4KIIα regulates insulin secretion and glucose homeostasis via a PKD-dependent pathway. Biophysics Reports, 2018, 4(1): 25-38. doi: 10.1007/s41048-018-0049-z

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PI4KIIα regulates insulin secretion and glucose homeostasis via a PKD-dependent pathway

doi: 10.1007/s41048-018-0049-z

Lunfeng Zhang^1,2,
Jiangmei Li^1,3,
Panpan Zhang³,
Zhen Gao^1,2,
Yingying Zhao^1,3,
Xinhua Qiao^1,2,
Chang Chen^{1,2,4
,
,}

1 National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
2 University of Chinese Academy of Sciences, Beijing 100049, China
3 Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China
4 Beijing Institute for Brain Disorders, Beijing 100069, China

Funds: This work was supported by the National Key Research and Development Program of China (2017YFA0504000, 2016YFC0903100), the National Natural Science Foundation of China (31570857, 31101021, and 81472839); the "863" National High-Technology Development Program of China (0A200202D03); the Novo Nordisk-Chinese Academy of Sciences Research Fund (NNCAS-2012-2); the Beijing Natural Science Foundation (7132156); Science and Technology Commission of Shanghai Municipality (15431903100); Personalized Medicines-Molecular Signature-based Drug Discovery and Development, the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA12020316).

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Corresponding author: Chang Chen,changchen@moon.ibp.ac.cn
Received Date: 29 January 2018
Rev Recd Date: 08 February 2018
Publish Date: 28 February 2018

Abstract

Abstract

Insulin release by pancreatic β cells plays a key role in regulating blood glucose levels in humans, and to understand the mechanism for insulin secretion may reveal therapeutic strategies for diabetes. We found that PI4KⅡα transgenic (TG) mice have abnormal glucose tolerance and higher serum glucose levels than wild-type mice. Glucose-stimulated insulin secretion was significantly reduced in both PI4KⅡα TG mice and PI4KⅡα-overexpressing pancreatic β cell lines. A proximity-based biotin labeling technique, BioID, was used to identify proteins that interact with PI4KⅡα, and the results revealed that PI4KⅡα interacts with PKD and negatively regulates its activity. The effect of PI4KⅡα on insulin secretion was completely rescued by altering PKD activity. PI4KⅡα overexpression also worsened glucose tolerance in streptozotocin/high-fat diet-induced diabetic mice by impairing insulin secretion. Our study has shed new light on PI4KⅡα function and mechanism in diabetes and identified PI4KⅡα as an important regulator of insulin secretion.

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References(49)

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