Impact of Conventional and Atypical MAPKs on the Development of Metabolic Diseases

Abstract

The family of mitogen-activated protein kinases (MAPKs) consists of fourteen members and has been implicated in regulation of virtually all cellular processes. MAPKs are divided into two groups, conventional and atypical MAPKs. Conventional MAPKs are further classified into four sub-families: extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK1, 2 and 3), p38 (α, β, γ, δ), and extracellular signal-regulated kinase 5 (ERK5). Four kinases, extracellular signal-regulated kinase 3, 4, and 7 (ERK3, 4 and 7) as well as Nemo-like kinase (NLK) build a group of atypical MAPKs, which are activated by different upstream mechanisms than conventional MAPKs. Early studies identified JNK1/2 and ERK1/2 as well as p38α as a central mediators of inflammation-evoked insulin resistance. These kinases have been also implicated in the development of obesity and diabetes. Recently, other members of conventional MAPKs emerged as important mediators of liver, skeletal muscle, adipose tissue, and pancreatic β-cell metabolism. Moreover, latest studies indicate that atypical members of MAPK family play a central role in the regulation of adipose tissue function. In this review, we summarize early studies on conventional MAPKs as well as recent findings implicating previously ignored members of the MAPK family. Finally, we discuss the therapeutic potential of drugs targeting specific members of the MAPK family.

Anti-Inflammatory and Anti-Diabetic Effect of Black Soybean Anthocyanins: Data from a Dual Cooperative Cellular System

“…Thus, inhibition of JNK and ERK signaling seemed to be a major mechanism for the suppression of obesity-induced inflammation by BSAn. Considering that JNK and ERK function as central mediators of inflammation-evoked insulin resistance in adipose tissue [ 29 ], inhibition of JNK and ERK signaling by BSAn could be associated with the effectiveness of BSAn for ameliorating obesity-induced insulin resistance.…”

Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

“…MAPKs are divided into four different sub-classes, including extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK1-3), p38 (α, β, γ, and δ), and ERK5. These kinases have involved in the appearance of insulin resistance [ 20 ]. In addition, there is another group of MAPKs, known as atypical kinases (ERK3/ERK4, NLK, and ERK7).…”

“…However, this group of proteins is poorly understood and needs more investigation. A recent review about all these groups of proteins was completed by the authors of [ 20 ].…”

“…The direct effects are involved in the control of metabolism, such as gluconeogenesis, in the control of protein synthesis, as well as in the mTORC1 signaling pathway. Furthermore, ERKs can directly regulate lipid homeostasis through the control of the sterol regulatory element-binding protein 1α and 2 (SREBP1α/2) or the hypoxia-inducing factor (HIF1α), among others, and reviewed by the authors of [ 20 , 23 ]. Regarding the indirect effects, ERKs can regulate the phosphorylation state of the protein synthesis initiation regulator, eIF4E, through MNK activation [ 26 , 27 ].…”

“…Like the rest of MAPKs, there are a great variety of substrates, including transcription factors (MEF2, Sap1, and others) and other kinases, such as the serum and glucocorticoid-induced protein kinase (SGK) [ 103 , 104 ]. Although it is necessary more knowledge, ERK5 activation mediates protection against diabetes and obesity, through different actions [ 20 ]. For instance, ERK5 induces an anti-inflammatory effect through the activation of PPARδ [ 105 ].…”