Obesity is not only closely related to insulin resistance but is one of the main factors leading to the formation of Type 2 Diabetes (T2D) too. The c-Jun N-terminal kinase (JNK) family is a member of the mitogen-activated protein kinase (MAPK) superfamily. JNK is also one of the most investigated signal transducers in obesity and insulin resistance. JNK-centric JNK signaling pathway can be activated by growth factors, cytokines, stress responses, and other factors. Many researches have identified that the activated phosphorylation JNK negatively regulates insulin signaling pathway in insulin resistance which can be simultaneously regulated by multiple signaling pathways related to the JNK signaling pathway. In this review, we provide an overview of the composition of the JNK signaling pathway, its regulation of insulin signaling pathway, and the relationship between the JNK signaling pathway and other pathways in insulin resistance.
It is well known that the cornea plays an important role in providing protection to the eye, but it is fragile and vulnerable. To clarify the biological effects and molecular mechanisms of the pituitary adenylate cyclase activating polypeptide (PACAP)-derived peptide MPAPO (named MPAPO) to promote corneal wound healing, we applied a mechanical method to establish a corneal injury model and analyzed the repair effects of MPAPO on corneal injury. MPAPO significantly promoted corneal wound repair in C57BL/6 mice. In addition, we established injury models of epithelial cells and trigeminal ganglion cells with H2O2. The results show that when the concentration of MPAPO is 1 μM, it can significantly promote the repair of injured corneal epithelial cells and the regeneration of trigeminal ganglion cell axons. MPAPO repairs epithelial cells through the promotion of GSK3β phosphorylation by binding to PAC1 and activating AKT. β-catenin escapes the phosphorylation of GSK3β and enters the nucleus to promote the expression of cyclin D1, accelerate cell cycle progression and promote cell proliferation. MPAPO promotes axonal regeneration by binding to the PAC1 receptor and activating adenylate cyclase activity, followed by the cAMP activation of protein kinase A activity and the promotion of CREB phosphorylation. Phosphorylated CREB promotes Bcl2 expression and axonal regeneration. In conclusion, our data support the role of MPAPO to facilitate corneal wound healing by promoting corneal epithelial cell proliferation and trigeminal ganglion cell axon regeneration.
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