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Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance

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Abstract

Obesity-induced low-grade inflammation (metaflammation) impairs insulin receptor signaling. This has been implicated in the development of insulin resistance. Insulin signaling in the target tissues is mediated by stress kinases such as p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, inhibitor of NF-kB kinase complex β (IKKβ), AMP-activated protein kinase, protein kinase C, Rho-associated coiled-coil containing protein kinase, and RNA-activated protein kinase. Most of these kinases phosphorylate several key regulators in glucose homeostasis. The phosphorylation of serine residues in the insulin receptor and IRS-1 molecule results in diminished enzymatic activity in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. This has been one of the key mechanisms observed in the tissues that are implicated in insulin resistance especially in type 2 diabetes mellitus (T2-DM). Identifying the specific protein kinases involved in obesity-induced chronic inflammation may help in developing the targeted drug therapies to minimize the insulin resistance. This review is focused on the protein kinases involved in the inflammatory cascade and molecular mechanisms and their downstream targets with special reference to obesity-induced T2-DM.

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Acknowledgements

This study was supported by a research grant to Dr. Kalyana C Nandipati from the LB692 Nebraska Tobacco Settlement Funds to Creighton University, and by the research Grants R01HL116042 and R01HL128063 from the National Institutes of Health, USA to DK Agrawal. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors have no other relevant affiliations or conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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  1. Department of Surgery, Creighton University School of Medicine, 601 N. 30th Street, Suite # 3700, Omaha, NE, 68131, USA

    Kalyana C. Nandipati

  2. Department of Clinical & Translational Science, Creighton University School of Medicine, 2500, California Plaza, Room # 510, Criss II, Omaha, NE, 68131, USA

    Kalyana C. Nandipati, Saravanan Subramanian & Devendra K. Agrawal

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  1. Kalyana C. Nandipati
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Nandipati, K.C., Subramanian, S. & Agrawal, D.K. Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance. Mol Cell Biochem 426, 27–45 (2017). https://doi.org/10.1007/s11010-016-2878-8

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