Tissue-specific regulation of insulin-PI3K/Akt, KEAP1-NRF2 and PKC/NF-κB signaling in high fat diet-fed and nicotinamide/streptozotocin-induced diabetic rats

Event Abstract Back to Event Tissue-specific regulation of insulin-PI3K/Akt, KEAP1-NRF2 and PKC/NF-κB signaling in high fat diet-fed and nicotinamide/streptozotocin-induced diabetic rats Der Jiun Ooi1* and Maznah Ismail2 1 Faculty of Dentistry, Mahsa University, Malaysia 2 Putra Malaysia University, Malaysia Background Type 2 diabetes mellitus (T2DM), a heterogeneous metabolic disorder, is due primarily to complex interplay of multiple inherited and acquired factors that adversely impair glucose metabolism. In particular, impaired insulin actions at multiple target tissues lead to eccentric glucose, lipid and redox homeostasis. While it is widely recognized that insulin resistance underlies the pathophysiology of T2DM, the complicated tissue-specific gene expression regulation and phenotypic association of the disease, particularly in diabetic animal model, remain largely under-studied. The present study aims to determine the correlated tissue-specific gene expression changes in experimental diabetic rat model. Methods The high fat diet-fed and nicotinamide/streptozotocin-induced mild diabetic (DIA) rats were used in the present study. Normal diet- (NOD) and high fat diet-fed (HFD) rats served as controls. The expressions of key genes involved in insulin-PI3K/Akt, KEAP1-NRF2 and PKC/NF-κB signaling, as well as correlation between gene expression changes, were profiled from white adipose, skeletal muscle, and liver tissues. The differential and non-differential molecular network interactions were further identified. Results Consistent with previous literature, statistical analyses revealed severe inflammation and perturbed metabolic functions in both HFD and DIA groups. Interestingly, potential tissue-specific compensatory antioxidant mechanisms were also observed across all the target tissues. Further dynamical analyses on differential and non-differential expression networks demonstrated tissue-specific modulations of inflammatory and antioxidant responses in relation to deranged insulin signaling. Conclusion The present study suggested tissue-specific and inter-tissue gene expression interactions in the mild diabetic rat model. Further studies and association with tissue-specific gene expression changes in human diabetic patients may further validate the use of present animal model to be verified fit for diabetes translational research purpose. Keywords: type 2 diabetes mellitus, tissue-specific gene expression, insulin-PI3K/Akt signaling, KEAP1-NRF2 signaling, PKC/NF-κB signaling Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Oral Presentation Topic: Metabolic diseases Citation: Ooi D and Ismail M (2019). Tissue-specific regulation of insulin-PI3K/Akt, KEAP1-NRF2 and PKC/NF-κB signaling in high fat diet-fed and nicotinamide/streptozotocin-induced diabetic rats. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00063 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 07 Nov 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Der Jiun Ooi, Faculty of Dentistry, Mahsa University, Jenjarum, Malaysia, ooiderjiun@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Der Jiun Ooi Maznah Ismail Google Der Jiun Ooi Maznah Ismail Google Scholar Der Jiun Ooi Maznah Ismail PubMed Der Jiun Ooi Maznah Ismail Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.