Nicotinamide Mononucleotide Prevents Free Fatty Acid-Induced Reduction in Glucose Tolerance by Decreasing Insulin Clearance
The NAD-dependent deacetylase SIRT1 improves β cell function. Accordingly, nicotinamide mononucleotide (NMN), the product of the rate-limiting step in NAD synthesis, prevents β cell dysfunction and glucose intolerance in mice fed a high-fat diet. The current study was performed to assess the effects...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/24/13224 |
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| author | Ashraf Nahle Yemisi Deborah Joseph Sandra Pereira Yusaku Mori Frankie Poon Hilda E. Ghadieh Aleksandar Ivovic Tejas Desai Simona S. Ghanem Suman Asalla Harrison T. Muturi Emelien M. Jentz Jamie W. Joseph Sonia M. Najjar Adria Giacca |
| author_facet | Ashraf Nahle Yemisi Deborah Joseph Sandra Pereira Yusaku Mori Frankie Poon Hilda E. Ghadieh Aleksandar Ivovic Tejas Desai Simona S. Ghanem Suman Asalla Harrison T. Muturi Emelien M. Jentz Jamie W. Joseph Sonia M. Najjar Adria Giacca |
| author_sort | Ashraf Nahle |
| collection | DOAJ |
| description | The NAD-dependent deacetylase SIRT1 improves β cell function. Accordingly, nicotinamide mononucleotide (NMN), the product of the rate-limiting step in NAD synthesis, prevents β cell dysfunction and glucose intolerance in mice fed a high-fat diet. The current study was performed to assess the effects of NMN on β cell dysfunction and glucose intolerance that are caused specifically by increased circulating free fatty acids (FFAs). NMN was intravenously infused, with or without oleate, in C57BL/6J mice over a 48-h-period to elevate intracellular NAD levels and consequently increase SIRT1 activity. Administration of NMN in the context of elevated plasma FFA levels considerably improved glucose tolerance. This was due not only to partial protection from FFA-induced β cell dysfunction but also, unexpectedly, to a significant decrease in insulin clearance. However, in conditions of normal FFA levels, NMN impaired glucose tolerance due to decreased β cell function. The presence of this dual action of NMN suggests caution in its proposed therapeutic use in humans. |
| first_indexed | 2024-03-10T03:58:04Z |
| format | Article |
| id | doaj.art-f88ba7de538c4a80adcd7d91c2eaac40 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:58:04Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f88ba7de538c4a80adcd7d91c2eaac402023-11-23T08:43:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241322410.3390/ijms222413224Nicotinamide Mononucleotide Prevents Free Fatty Acid-Induced Reduction in Glucose Tolerance by Decreasing Insulin ClearanceAshraf Nahle0Yemisi Deborah Joseph1Sandra Pereira2Yusaku Mori3Frankie Poon4Hilda E. Ghadieh5Aleksandar Ivovic6Tejas Desai7Simona S. Ghanem8Suman Asalla9Harrison T. Muturi10Emelien M. Jentz11Jamie W. Joseph12Sonia M. Najjar13Adria Giacca14Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaCenter for Diabetes and Endocrine Research, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USADepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaCenter for Diabetes and Endocrine Research, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USADepartment of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USADepartment of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USASchool of Pharmacy, University of Waterloo, Kitchener, ON N2G 1C5, CanadaSchool of Pharmacy, University of Waterloo, Kitchener, ON N2G 1C5, CanadaCenter for Diabetes and Endocrine Research, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USADepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaThe NAD-dependent deacetylase SIRT1 improves β cell function. Accordingly, nicotinamide mononucleotide (NMN), the product of the rate-limiting step in NAD synthesis, prevents β cell dysfunction and glucose intolerance in mice fed a high-fat diet. The current study was performed to assess the effects of NMN on β cell dysfunction and glucose intolerance that are caused specifically by increased circulating free fatty acids (FFAs). NMN was intravenously infused, with or without oleate, in C57BL/6J mice over a 48-h-period to elevate intracellular NAD levels and consequently increase SIRT1 activity. Administration of NMN in the context of elevated plasma FFA levels considerably improved glucose tolerance. This was due not only to partial protection from FFA-induced β cell dysfunction but also, unexpectedly, to a significant decrease in insulin clearance. However, in conditions of normal FFA levels, NMN impaired glucose tolerance due to decreased β cell function. The presence of this dual action of NMN suggests caution in its proposed therapeutic use in humans.https://www.mdpi.com/1422-0067/22/24/13224type 2 diabetesinsulin resistanceinsulin clearanceSIRTsglucose tolerancefree fatty acids |
| spellingShingle | Ashraf Nahle Yemisi Deborah Joseph Sandra Pereira Yusaku Mori Frankie Poon Hilda E. Ghadieh Aleksandar Ivovic Tejas Desai Simona S. Ghanem Suman Asalla Harrison T. Muturi Emelien M. Jentz Jamie W. Joseph Sonia M. Najjar Adria Giacca Nicotinamide Mononucleotide Prevents Free Fatty Acid-Induced Reduction in Glucose Tolerance by Decreasing Insulin Clearance International Journal of Molecular Sciences type 2 diabetes insulin resistance insulin clearance SIRTs glucose tolerance free fatty acids |
| title | Nicotinamide Mononucleotide Prevents Free Fatty Acid-Induced Reduction in Glucose Tolerance by Decreasing Insulin Clearance |
| title_full | Nicotinamide Mononucleotide Prevents Free Fatty Acid-Induced Reduction in Glucose Tolerance by Decreasing Insulin Clearance |
| title_fullStr | Nicotinamide Mononucleotide Prevents Free Fatty Acid-Induced Reduction in Glucose Tolerance by Decreasing Insulin Clearance |
| title_full_unstemmed | Nicotinamide Mononucleotide Prevents Free Fatty Acid-Induced Reduction in Glucose Tolerance by Decreasing Insulin Clearance |
| title_short | Nicotinamide Mononucleotide Prevents Free Fatty Acid-Induced Reduction in Glucose Tolerance by Decreasing Insulin Clearance |
| title_sort | nicotinamide mononucleotide prevents free fatty acid induced reduction in glucose tolerance by decreasing insulin clearance |
| topic | type 2 diabetes insulin resistance insulin clearance SIRTs glucose tolerance free fatty acids |
| url | https://www.mdpi.com/1422-0067/22/24/13224 |
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