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

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...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 2017-02, Vol.426 (1-2), p.27-45
Main Authors: Nandipati, Kalyana C., Subramanian, Saravanan, Agrawal, Devendra K.
Format: Article
Language:English
Subjects:
Analysis
Animals
B cells
Biochemistry
Biomedical and Life Sciences
Cardiology
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - pathology
Enzymatic activity
Enzymes
Glucose
Humans
Inflammation
Inflammation - metabolism
Inflammation - pathology
Insulin Resistance
Kinases
Life Sciences
Medical Biochemistry
Mitogens
Obesity
Obesity - metabolism
Obesity - pathology
Oncology
Phosphatidylinositol 3-Kinases - metabolism
Protein kinases
Protein Kinases - metabolism
Signal Transduction
Studies
Type 2 diabetes
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Summary: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.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-016-2878-8