title: Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance.
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.
authors.affiliation: Department of Surgery, Creighton University School of Medicine, 601 N. 30th Street, Suite # 3700, Omaha, NE, 68131, USA. Kalyana.Nandipati@alegent.org.|Department of Clinical & Translational Science, Creighton University School of Medicine, 2500, California Plaza, Room # 510, Criss II, Omaha, NE, 68131, USA. Kalyana.Nandipati@alegent.org.
authors.forename: Kalyana C
authors.initials: KC
authors.lastname: Nandipati
authors.affiliation: Department of Clinical & Translational Science, Creighton University School of Medicine, 2500, California Plaza, Room # 510, Criss II, Omaha, NE, 68131, USA.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: Department of Clinical & Translational Science, Creighton University School of Medicine, 2500, California Plaza, Room # 510, Criss II, Omaha, NE, 68131, USA.
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011494:Protein Kinases; D019869:Phosphatidylinositol 3-Kinases
keywords: Inflammation; Insulin resistance; Obesity; Protein kinases