Ablation of Elovl6 protects pancreatic islets from high-fat diet-induced impairment of insulin secretion |
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Authors: | Nie Tang Takashi Matsuzaka Marii Suzuki Yuta Nakano Hui Zao Tomotaka Yokoo Noriko Suzuki-Kemuriyama Motoko Kuba Yuka Okajima Yoshinori Takeuchi Kazuto Kobayashi Hitoshi Iwasaki Shigeru Yatoh Akimitsu Takahashi Hiroaki Suzuki Hirohito Sone Masako Shimada Yoshimi Nakagawa Naoya Yahagi Nobuhiro Yamada Hitoshi Shimano |
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Institution: | 1. Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan;2. Experimental Animal Laboratory, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka City, Saitama 350-1241, Japan;3. Department of Internal Medicine, Faculty of Medicine, Niigata University, 1-754 Asahimachi, Niigata, Niigata 951-8510, Japan |
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Abstract: | ELOVL family member 6, elongation of very long-chain fatty acids (Elovl6) is a microsomal enzyme that regulates the elongation of C12–16 saturated and monounsaturated fatty acids and is related to the development of obesity-induced insulin resistance via the modification of the fatty acid composition. In this study, we investigated the role of systemic Elovl6 in the pancreatic islet and β-cell function. Elovl6 is expressed in both islets and β-cell lines. In mice fed with chow, islets of the Elovl6−/− mice displayed normal architecture and β-cell mass compared with those of the wild-type mice. However, when fed a high-fat, high-sucrose (HFHS) diet, the islet hypertrophy in response to insulin resistance observed in normal mice was attenuated and glucose-stimulated insulin secretion (GSIS) increased in the islets of Elovl6−/− mice compared with those of the wild-type mice. Enhanced GSIS in the HFHS Elovl6−/− islets was associated with an increased ATP/ADP ratio and the suppression of ATF-3 expression. Our findings suggest that Elovl6 could be involved in insulin secretory capacity per β-cell and diabetes. |
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Keywords: | Fatty acid Obesity Type 2 diabetes Insulin Islet β-cell |
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