| First Author | Cercillieux A | Year | 2022 |
| Journal | Mol Metab | Volume | 66 |
| Pages | 101605 | PubMed ID | 36165811 |
| Mgi Jnum | J:330011 | Mgi Id | MGI:7355559 |
| Doi | 10.1016/j.molmet.2022.101605 | Citation | Cercillieux A, et al. (2022) Nicotinamide riboside kinase 1 protects against diet and age-induced pancreatic beta-cell failure. Mol Metab 66:101605 |
| abstractText | OBJECTIVE: Disturbances in NAD(+) metabolism have been described as a hallmark for multiple metabolic and age-related diseases, including type 2 diabetes. While alterations in pancreatic beta-cell function are critical determinants of whole-body glucose homeostasis, the role of NAD(+) metabolism in the endocrine pancreas remains poorly explored. Here, we aimed to evaluate the role of nicotinamide riboside (NR) metabolism in maintaining NAD(+) levels and pancreatic beta-cell function in pathophysiological conditions. METHODS: Whole body and pancreatic beta-cell-specific NRK1 knockout (KO) mice were metabolically phenotyped in situations of high-fat feeding and aging. We also analyzed pancreatic beta-cell function, beta-cell mass and gene expression. RESULTS: We first demonstrate that NRK1, the essential enzyme for the utilization of NR, is abundantly expressed in pancreatic beta-cells. While NR treatment did not alter glucose-stimulated insulin secretion in pancreatic islets from young healthy mice, NRK1 knockout mice displayed glucose intolerance and compromised beta-cells response to a glucose challenge upon high-fat feeding or aging. Interestingly, beta cell dysfunction stemmed from the functional failure of other organs, such as liver and kidney, and the associated changes in circulating peptides and hormones, as mice lacking NRK1 exclusively in beta-cells did not show altered glucose homeostasis. CONCLUSIONS: This work unveils a new physiological role for NR metabolism in the maintenance of glucose tolerance and pancreatic beta-cell function in high-fat feeding or aging conditions. |
