Effects of Epac1 on Diabetic Retinal Inflammation Journal of Health Disparities Research and Practice Volume 12 Issue 2019 STEP-UP Special Issue Article 51 © Center for Health Disparities Research, School of Public Health, University of Nevada, Las Vegas 2018 Effects of Epac1 on Diabetic Retinal Inflammation Claire Hawthorne Jena Steinle, PhD , Wayne State University School of Medicine Youde Jiang, MS , Wayne State University School of Medicine See next page for additional authors Follow this and additional works at: https://digitalscholarship.unlv.edu/jhdrp Part of the Medicine and Health Sciences Commons Recommended Citation Hawthorne, Claire; Steinle, PhD, Jena; Jiang, MS, Youde; and Liu, PhD, Li (2018) "Effects of Epac1 on Diabetic Retinal Inflammation," Journal of Health Disparities Research and Practice: Vol 12 : Iss , Article 51 Available at: https://digitalscholarship.unlv.edu/jhdrp/vol12/iss4/51 This Article is protected by copyright and/or related rights It has been brought to you by Digital Scholarship@UNLV with permission from the rights-holder(s) You are free to use this Article in any way that is permitted by the copyright and related rights legislation that applies to your use For other uses you need to obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself This Article has been accepted for inclusion in Journal of Health Disparities Research and Practice by an authorized administrator of Digital Scholarship@UNLV For more information, please contact digitalscholarship@unlv.edu Effects of Epac1 on Diabetic Retinal Inflammation Abstract An ever-growing body of research suggests that inflammation is one of the primary causes of diabetic retinopathy, as the inflammation can lead to insulin resistance Beta-adrenergic receptor agonists can reduce the inflammation in human retinal endothelial cells (HRECs), but are not a viable treatment due to systemic effects Epac1 lies downstream of beta-adrenergic receptor signaling, and it may have the capability to reduce inflammation by acting as an alternative pathway for beta-adrenergic receptor agonists to block inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1B) We hypothesized that the Epac1 agonist will decrease cytokine levels, leading to improved insulin signal transduction in the retina HRECs were grown in normal (5mM) or high glucose (25mM) Some cells were not treated with the Epac1 agonist and serve as controls Western blotting was done using primary antibodies for total and phosphorylated insulin receptor substrate-1 (IRS-1), insulin receptor (IR) and Akt, as well as beta actin as a control for loading Anti-Rabbit IgG/HRP was used for secondary antibodies ELISA analyses were done for protein levels of TNF-alpha and IL-1B We are not done with data analyses, but we expect to find that Epac1 will increase insulin receptor and Akt phosphorylation, while reducing TNF-alpha and IL-1B levels Keywords Diabetic retinopathy; Epac1; inflammation; TNF-alpha; Western blot Cover Page Footnote The STEP-UP HS program is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health Grant: 2R25DK078382-12 Authors Claire Hawthorne; Jena Steinle, PhD; Youde Jiang, MS; and Li Liu, PhD This article is available in Journal of Health Disparities Research and Practice: https://digitalscholarship.unlv.edu/ jhdrp/vol12/iss4/51 72 Effects of Epac1 on Diabetic Retinal Inflammation Hawthorne, Steinle, Jiang, and Liu Journal of Health Disparities Research and Practice Volume 12, STEP-UP Special Issue, Summer 2019, pp 72 © 2011 Center for Health Disparities Research School of Public Health University of Nevada, Las Vegas Effects of Epac1 on Diabetic Retinal Inflammation Claire Hawthorne Jena Steinle, PhD, Wayne State University School of Medicine Youde Jiang, MS, Wayne State University School of Medicine Li Liu, PhD, Wayne State University School of Medicine Coordinating Center: Stanford University ABSTRACT An ever-growing body of research suggests that inflammation is one of the primary causes of diabetic retinopathy, as the inflammation can lead to insulin resistance Beta-adrenergic receptor agonists can reduce the inflammation in human retinal endothelial cells (HRECs), but are not a viable treatment due to systemic effects Epac1 lies downstream of beta-adrenergic receptor signaling, and it may have the capability to reduce inflammation by acting as an alternative pathway for beta-adrenergic receptor agonists to block inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1B) We hypothesized that the Epac1 agonist will decrease cytokine levels, leading to improved insulin signal transduction in the retina HRECs were grown in normal (5mM) or high glucose (25mM) Some cells were not treated with the Epac1 agonist and serve as controls Western blotting was done using primary antibodies for total and phosphorylated insulin receptor substrate-1 (IRS-1), insulin receptor (IR) and Akt, as well as beta actin as a control for loading Anti-Rabbit IgG/HRP was used for secondary antibodies ELISA analyses were done for protein levels of TNF-alpha and IL-1B We are not done with data analyses, but we expect to find that Epac1 will increase insulin receptor and Akt phosphorylation, while reducing TNF-alpha and IL-1B levels Keywords: Diabetic retinopathy, Epac1, inflammation, TNF-alpha, Western blot ACKNOWLEDGEMENTS The STEP-UP HS program is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health Grant: 2R25DK078382-12 Journal of Health Disparities Research and Practice Volume 12, STEP-UP Special Issue, Summer 2019 http://digitalscholarship.unlv.edu/jhdrp/ Follow on Facebook: Health.Disparities.Journal Follow on Twitter: @jhdrp .. .Effects of Epac1 on Diabetic Retinal Inflammation Abstract An ever-growing body of research suggests that inflammation is one of the primary causes of diabetic retinopathy, as the inflammation. .. Las Vegas Effects of Epac1 on Diabetic Retinal Inflammation Claire Hawthorne Jena Steinle, PhD, Wayne State University School of Medicine Youde Jiang, MS, Wayne State University School of Medicine... available in Journal of Health Disparities Research and Practice: https://digitalscholarship.unlv.edu/ jhdrp/vol12/iss4/51 72 Effects of Epac1 on Diabetic Retinal Inflammation Hawthorne, Steinle,