DGK is a key enzyme in glucose uptake in skeletal
DGKδ is a key enzyme in glucose uptake in skeletal muscle. Chibalin et al. demonstrated that a decrease in DGKδ expression increases the severity of type 2 diabetes . Additionally, DGKδ expression was increased in people who exhibited enhanced insulin sensitivity after exercise training . Fritz et al. also reported that exercise training induces improvements in insulin sensitivity and increases DGKδ gene expression in type 2 diabetes patients . Recently, we have found that myristic L-Mimosine (14:0) in C2C12 myotubes significantly increases DGKδ levels and enhances glucose uptake in a DGKδ-dependent manner [24,25]. Moreover, our recent study demonstrated that myristic acid increases DGKδ levels in skeletal muscle of NSY type 2 diabetes-model mice and reduced insulin-responsive blood glucose levels of the mice . These studies strongly indicate that up-regulation of DGKδ is important for prevention and treatment of type 2 diabetes. On the other hand, a previous study suggested that excessive loss of muscle mass in older adults with type 2 diabetes may result in poor muscle strength, functional limitations and physical disability . Therefore, for the treatment of type 2 diabetes, it is important to not only improve glucose homeostasis in skeletal muscle but also to increase muscle mass. The present study indicated that DGKδ is involved in C2C12 myogenic differentiation. Therefore, the elucidation of the role of DGKδ in adult myogenesis might provide useful information for therapeutic treatment of type 2 diabetes.
Conflicts of interest
Acknowledgement The present study was supported in part by KAKENHI (Grant Numbers 15K18859 and 17K08271) and a research grant from Shimane University.
Immune rejection in cancer Despite the advances in the area, cancer still represents the most important cause of death in developed countries together with cardiovascular disease (Siegel et al., 2016). The main cause of mortality due to cancer is the metastatic spread to other organs. Metastasis occurs when tumor cells acquire invasive features and the ability to escape from antitumor immunity (Massague and Obenauf, 2016). After initial treatments tumors can remain dormant for years thanks to the continuous surveillance of the immune system. Eventually, some tumors evolve to acquire immune suppressive properties, escape from T cell attack and re-emerge in different locations (Dunn et al., 2004). Evading immune response is recognized as one of the hallmarks of cancer (Hanahan and Weinberg, 2011) and represents one of the more active areas of research in cancer. After many years of trial and error, the clinical progress in the field of immunotherapy against cancer has recently provided great success (Pardoll, 2015). Over the past years, the cytotoxic T lymphocyte (CTL) response has been identified as one of the most powerful and effective links in this vast network and the blockage of the CTL-mediated cytotoxic program by the tumor millieu appears as the main mechanism for tumor immune evasion. The so-called immune checkpoints have emerged as potent regulators of cytotoxic responses (Topalian et al., 2015). Those include receptors and their ligands, as well as intracellular molecules, which act by limiting immune response. Healthy tissues and hematopoietic cells depend on the immune checkpoints to avoid destruction during immune attack. Tumors hijack this strategy, designed to prevent self-damage of healthy organs, to evade immune destruction. Immunological checkpoints inhibitors such as anti-CTL-4, anti-PD-1 or anti-PDL1 together with stimulators of co-activation mechanisms have proven to overcome tumor induce-tolerance. Although spectacular clinical remissions have consistently been observed in some tumors like melanoma when boosting CTL responses with checkpoint inhibitory antibodies, the efficacy of immunotherapies in the treatment of solid tumors still remains below a threshold that justified their use in the general patient population.