Normal pancreatic β-cell function in mice with <i>RIP-Cre</i>-mediated inactivation of p62/SQSTM1

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Author(s)

    • Honda Akira
    • Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
    • Komiya Koji
    • Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
    • Hara Akemi
    • Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan|Center for Identification of Diabetic Therapeutic Targets, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
    • Fukunaka Ayako
    • Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan|Laboratory of Developmental Biology and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan
    • Suzuki Luka
    • Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
    • Miyatsuka Takeshi
    • Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan|Center for Identification of Diabetic Therapeutic Targets, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
    • Ogihara Takeshi
    • Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
    • Fujitani Yoshio
    • Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan|Laboratory of Developmental Biology and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan
    • Watada Hirotaka
    • Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan|Center for Identification of Diabetic Therapeutic Targets, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan|Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan|Sportology Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan

Abstract

<p>Recent studies have suggested that decreased pancreatic β-cell function and mass are common features of patients with type 2 diabetes mellitus. Pancreatic β-cell homeostasis is regulated by various types of signaling molecules and stress responses. Sequestosome 1/p62 (SQSTM1, hereafter referred to as p62) is a ubiquitin-binding adaptor protein involved in cell signaling, oxidative stress, and autophagy. Because p62 appears to play an important role in maintaining mitochondrial quality control, it is possible that the loss of <i>p62</i> in pancreatic β cells contributes to mitochondrial dysfunction, and thus leading to impaired glucose tolerance. In this study we investigated the physiological roles of p62 by inactivating <i>p62</i> in a β-cell specific manner. We found that firstly, rat insulin-2 promoter-<i>Cre</i> (<i>RIP-Cre</i>)-mediated <i>p62</i> inactivation did not cause body weight gain, although ubiquitous inactivation of <i>p62</i> was previously shown to result in severe obesity. Secondly, we found no gross structural disorganization of the islets of <i>p62</i>-deficient mice. Consistent with normal islet morphology, no impairment in glucose tolerance was observed in mice with <i>RIP-Cre</i>-mediated <i>p62</i> deletion. These results suggest that <i>p62</i> is dispensable for normal islet organization and β-cell function.</p>

Journal

  • Endocrine Journal

    Endocrine Journal 65(1), 83-89, 2018

    The Japan Endocrine Society

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