VMAT2 safeguards beta-cells against dopamine cytotoxicity under high-fat diet induced stress
figureposted on 21.08.2020 by Ada Admin, Daisuke Sakano, Fumiya Uefune, Hiraku Tokuma, Yuki Sonoda, Kumi Matsuura, Naoki Takeda, Naomi Nakagata, Kazuhiko Kume, Nobuaki Shiraki, Shoen Kume
Figures are generally photos, graphs and static images that would be represented in traditional pdf publications.
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 (βVmat2KO) mice show elevated insulin secretion levels in response to glucose stimulation. Under prolonged high-fat diet feedings, the βVmat2KO 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.