Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle

Ruby, Maxwell A, Riedl, Isabelle, Massart, Julie, Åhlin, Marcus and Zierath, Juleen R (2017) Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle. AJP: Endocrinology and Metabolism, 313 (4). E483-E491. ISSN 0193-1849

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    Abstract

    Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo. PKN2 knockdown in vitro decreased insulin-stimulated glucose uptake, incorporation into glycogen, and oxidation. PKN2 siRNA increased 5′-adenosine monophosphate-activated protein kinase (AMPK) signaling while stimulating fatty acid oxidation and incorporation into triglycerides and decreasing protein synthesis. At the transcriptional level, PKN2 knockdown increased expression of PGC-1α and SREBP-1c and their target genes. In mature skeletal muscle, in vivo PKN2 knockdown decreased glucose uptake and increased AMPK phosphorylation. Thus, PKN2 alters key signaling pathways and transcriptional networks to regulate glucose and lipid metabolism. Identification of PKN2 as a novel regulator of insulin and AMPK signaling may provide an avenue for manipulation of skeletal muscle metabolism.

    Item Type: Article
    Additional Information: Copyright © 2017 the American Physiological Society.
    Uncontrolled Keywords: adenylate kinase,animals,fatty acids,gene knockdown techniques,glucose,glycogen,humans,in vitro techniques,insulin resistance,lipid metabolism,male,mice,mice, inbred c57bl,muscle fibers, skeletal,muscle, skeletal,peroxisome proliferator-activated receptor gamma coactivator 1-alpha,phosphorylation,protein biosynthesis,protein kinase c,quadriceps muscle,signal transduction,sterol regulatory element binding protein 1,triglycerides,journal article
    Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
    Depositing User: Pure Connector
    Date Deposited: 19 Jan 2018 12:30
    Last Modified: 11 Jul 2019 16:34
    URI: https://ueaeprints.uea.ac.uk/id/eprint/66019
    DOI: 10.1152/ajpendo.00147.2017

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