| First Author | Sakano D | Year | 2020 |
| Journal | Diabetes | Volume | 69 |
| Issue | 11 | Pages | 2377-2391 |
| PubMed ID | 32826296 | Mgi Jnum | J:295948 |
| Mgi Id | MGI:6454202 | Doi | 10.2337/db20-0207 |
| Citation | Sakano D, et al. (2020) VMAT2 Safeguards Beta-Cells Against Dopamine Cytotoxicity Under High-Fat Diet Induced Stress. Diabetes 69(11):2377-2391 |
| abstractText | Vesicular monoamine transporter 2 (VMAT2) uptakes cytoplasmic monoamines into vesicles for storage. VMAT2 plays a role in modulating insulin release by regulating dopamine levels in the pancreas, although the exact mechanism remains elusive. We found that VMAT2 expression in beta-cells specifically increases under high blood glucose conditions. The islets isolated from beta-cell specific Vmat2 knock-out (betaVmat2KO) mice show elevated insulin secretion levels in response to glucose stimulation. Under prolonged high-fat diet feedings, the betaVmat2KO mice exhibit impaired glucose and insulin tolerance and progressive beta-cell dysfunction. We demonstrate here that VMAT2 uptakes dopamine to protect it from degradation by monoamine oxidase, thereby safeguarding beta-cells from excess reactive oxygen species (ROS) exposure. When under high demand for insulin secretion, the absence of VMAT2 leads to elevated ROS in beta-cells, which accelerates beta-cell dedifferentiation and beta-cell loss. Therefore, VMAT2 controls the amount of dopamine in beta-cells thereby protecting pancreatic beta-cells from excessive oxidative stress. |
