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Insulin Resistance and Glucose Regulation
Published in Awanish Kumar, Ashwini Kumar, Diabetes, 2020
Reduction in IR expression has further been stated in obese mice models with hepatic steatosis. Further, it has been found that saturated fatty acids reduce the mRNA and protein level of IR in cell lines of hepatocyte and skeletal muscle. Some reports also suggest that IR expression is inversely related to protein kinase C (PKCε isoform) in obese animal models. PKCε has been found to impair the HMGA1 which is the major transcription factor of the IR gene. In a breakthrough study, it was reported that lipids phosphorylate PKCε through palmitoylation. Phosphorylated PKCε in turn impairs HMGA1 which finally reduces the IR expression leading to a significant decrease in insulin sensitivity [17].
Cognition Enhancers
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Ramneek Kaur, Rashi Rajput, Sachin Kumar, Harleen Kaur, R. Rachana, Manisha Singh
Various apoptosis inhibitors are known till now, but none has been approved for clinical use because inhibiting the cell death is quite questionable. But, the idea of utilizing CE as apoptosis inhibitors is not dead. As there are few evidences that support this theory like—PKCγ protein is known to inhibit apoptosis (Basu and Sivaprasad, 2007; Ding et al., 2002; Gillespie et al., 2005; Okhrimenko et al., 2005) and it raises the view of using the activators of PKCγ like DCP-LA as inhibitors of central nervous system (CNS) apoptosis. Similarly, isozymes like PKCα, β, βII, and γ also participate in this process and are overexpressed in cochlea hair cells during the regeneration phase after the damage caused by glutamate analog AMPA (Lerner-Natoli et al., 1997). Among the isozymes, PKCδ and PKCε are the important ones which determine the struggle of life and death between apoptosis and growth.
Type 2 Diabetes in Childhood
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
While the mechanism for the IR induced by ectopic fat deposition has not been fully elucidated, diacylglycerol (DAG) has been implicated. DAG is a signaling intermediate for protein kinase-C (PKC) and appears to be increased in the intracellular compartment of patients with higher IMCL and in patients with NAFLD. DAG appears to promote IR through novel PKC pathways involved in glucose uptake and in nonoxidative glucose metabolism. Hepatic DAG levels were elevated in rats with diet-induced NAFLD and IR. There was increased translocation of the primary novel PKC isoform in liver, protein kinase-Cε (PKCε) to the plasma membrane, where it bound and inhibited the intracellular tyrosine kinase activity of the insulin receptor. This led to reduced insulin-mediated glycogenesis and suppression of gluconeogenesis (Figure 14.2) [12]. In rats with NAFLD and chemically induced downregulation of PKC, hepatic insulin activity was normal despite high DAG levels and hepatic lipid content [12].
A comparison expression analysis of CXCR4, CXCL9 and Caspase-9 in dermal vascular endothelial cells between keloids and normal skin on chemotaxis and apoptosis
Published in Journal of Plastic Surgery and Hand Surgery, 2022
Xinhang Dong, Mingzi Zhang, Yuanjing Chen, Chengcheng Li, Youbin Wang, Xiaolei Jin
To some extent, keloids are an inflammatory disease involving the reticular dermis layer, and injuries of the reticular dermis and abnormal wound healing are major causes of the disease. Studies have shown that pro-inflammatory cytokines such as TNF-α (tumor necrosis factor-α), IL-1α (interleukin-1α), IL-1β (interleukin-1β) and IL-6 (interleukin-6) in keloid tissue are highly expressed, which could promote chronic inflammation and cause invasive growth of keloids [17]. As it is shown in the KEGG pathway analysis from Enrichr, inflammatory mediator regulation of TRP channels is significantly enriched in the KEGG pathway, including up-regulated DEGs of PRKCG, PRKCE, TRPV4, TRPV2, CALML4, ADCY1 and PRKACB. In this process, a large number of blood vessels are formed, while the functions are not complete. Moreover, due to the increase of blood vessel permeability and the induction of chemokines, a great number of inflammatory factors accumulate in the extracellular matrix, which is consistent with the high inflammation status shown by the HE staining results.
Claudin-18.2 as a therapeutic target in cancers: cumulative findings from basic research and clinical trials
Published in Tissue Barriers, 2022
Daisuke Kyuno, Akira Takasawa, Kumi Takasawa, Yusuke Ono, Tomoyuki Aoyama, Kazufumi Magara, Yuna Nakamori, Ichiro Takemasa, Makoto Osanai
Claudin-18.2 is regulated at the transcriptional level via PKC signaling pathways in human gastric cancer,34 pancreatic cancer, and normal pancreatic duct epithelial cells (HPDEs).59 Claudin-18.2 mRNA and claudin-18 protein are markedly induced by the PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) in well- and moderately differentiated human pancreatic cancer cell lines and HPDEs transfected with the human telomerase reverse transcriptase (hTERT) gene. In pancreatic cancer cell lines, TPA-induced claudin-18 expression is localized on apical and basolateral cell surfaces. The PKC family contains at least 12 different isozymes. Activation of PKCα, PKCδ, and PKCε has been reported to be associated with the upregulation of claudin-18 in human pancreatic cancer cell lines, whereas PKCα, PKCδ, and PKCθ activation has been associated with the upregulation of claudin-18 in hTERT-transfected HPDEs.59 Furthermore, the increase in TPA-induced claudin-18 expression is enhanced by DNA demethylation. Consequently, the regulation of claudin-18.2 is correlated with genomic hypomethylation of promoter CpG islands.6
PVAT targets VSMCs to regulate vascular remodelling: angel or demon
Published in Journal of Drug Targeting, 2021
Yin-Yu Zhang, Ya-Ning Shi, Neng Zhu, Tan-Jun Zhao, Yi-Jie Guo, Duan-Fang Liao, Ai-Guo Dai, Li Qin
Resistin is a proinflammatory adipokine that plays an important role in the development of insulin resistance, which is associated with obesity and diabetes [96]. Currently, there is increasing evidence that resistin is also involved in the pathological process of cardiovascular diseases, including inflammatory response [97], endothelial dysfunction [98], angiogenesis [99] and VSMCs dysfunction. Studies have shown that the guanine exchange factor ARF nucleotide-binding site opener (ARNO) participates in resistin-induced VSMCs phenotype conversion by activating p38 MAPK and JNK/AP-1 pathways, and causes VSMCs to migrate and produce MMP-2 [100]. Resistin can also stimulate the production of ROS through PKCε-mediated NADPH oxidase (Nox) activation, which leads to VSMCs dysfunction, promotes the release of inflammatory cytokines TNF-α and IL-1β, and aggravates carotid artery intimal hyperplasia in mice. Targeting the PKCε-Nox pathway may be a novel strategy for the treatment of complications of resistin-related atherosclerosis [101].