应用荧光寿命成像显微镜监测胰岛中的葡萄糖代谢。
Application of fluorescence lifetime imaging microscopy to monitor glucose metabolism in pancreatic islets .
作者信息
Wang Zhongying, Archang Maani, Gurlo Tatyana, Wong Elaine, Fraser Scott E, Butler Peter C
机构信息
Larry L. Hillblom Islet Research Center, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Department of Biological Sciences, Bridge Institute, David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA.
出版信息
Biomed Opt Express. 2023 Jul 19;14(8):4170-4178. doi: 10.1364/BOE.493722. eCollection 2023 Aug 1.
Glucose stimulated insulin secretion is mediated by glucose metabolism via oxidative phosphorylation generating ATP that triggers membrane depolarization and exocytosis of insulin. In stressed beta cells, glucose metabolism is remodeled, with enhanced glycolysis uncoupled from oxidative phosphorylation, resulting in the impaired glucose-mediated insulin secretion characteristic of diabetes. Relative changes in glycolysis and oxidative phosphorylation can be monitored in living cells using the 3-component fitting approach of fluorescence lifetime imaging microscopy (FLIM). We engrafted pancreatic islets onto the iris to permit in vivo FLIM monitoring of the trajectory of glucose metabolism. The results show increased oxidative phosphorylation of islet cells (∼90% beta cells) in response to hyperglycemia; in contrast red blood cells traversing the islets maintained exclusive glycolysis as expected in the absence of mitochondria.
葡萄糖刺激的胰岛素分泌是由葡萄糖通过氧化磷酸化进行代谢介导的，氧化磷酸化产生ATP，触发膜去极化和胰岛素的胞吐作用。在应激的β细胞中，葡萄糖代谢发生重塑，糖酵解增强且与氧化磷酸化解偶联，导致糖尿病特有的葡萄糖介导的胰岛素分泌受损。使用荧光寿命成像显微镜（FLIM）的三组分拟合方法可以在活细胞中监测糖酵解和氧化磷酸化的相对变化。我们将胰岛移植到虹膜上，以便在体内通过FLIM监测葡萄糖代谢轨迹。结果显示，响应高血糖时，胰岛细胞（约90%为β细胞）的氧化磷酸化增加；相比之下，穿过胰岛的红细胞如预期的那样在没有线粒体的情况下维持专一的糖酵解。
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