@article{3d335ee639e2419990fb399e68c1d161,
title = "Live-cell imaging of glucose-induced metabolic coupling of β and α cell metabolism in health and type 2 diabetes",
abstract = "Type 2 diabetes is characterized by β and α cell dysfunction. We used phasor-FLIM (Fluorescence Lifetime Imaging Microscopy) to monitor oxidative phosphorylation and glycolysis in living islet cells before and after glucose stimulation. In healthy cells, glucose enhanced oxidative phosphorylation in β cells and suppressed oxidative phosphorylation in α cells. In Type 2 diabetes, glucose increased glycolysis in β cells, and only partially suppressed oxidative phosphorylation in α cells. FLIM uncovers key perturbations in glucose induced metabolism in living islet cells and provides a sensitive tool for drug discovery in diabetes.",
author = "Zhongying Wang and Tatyana Gurlo and Matveyenko, {Aleksey V.} and David Elashoff and Peiyu Wang and Madeline Rosenberger and Junge, {Jason A.} and Stevens, {Raymond C.} and White, {Kate L.} and Fraser, {Scott E.} and Butler, {Peter C.}",
note = "Funding Information: Human islets and single islet cells. Human pancreatic islets were provided by the National Institution of Diabetes and Digestive and Kidney Diseases (NIDDK) funded Integrated Islet Distribution Program (IIDP) at City of Hope, National Institute of Health (NIH) Grant # 2UC4DK098085. The characteristics of islet donors are listed in Supplementary Table 2. Human islets were maintained in suspension in RPMI 1640 medium with 5.5 mM glucose supplemented with 100 IU/ml penicillin/streptomycin and 10% fetal bovine serum at 37 °C in a humidified 5% CO2 atmosphere. Islets were cultured in suspension for 4–6 d after isolation before plating on ibidi-slide 8 well with grid. Whole islets (80–100 µM diameter) were plated at a density 4–6 per well, imaging was performed 3 days after plating. Slides were precoated with extracellular matrix by growing human bladder cell carcinoma HTB-9 (human bladder cell carcinoma line 5367, available from ATCC) to a confluence and then lysed by 10 min exposure to 20 mM NH4OH. Funding Information: These studies were supported by the United States Public Health Services National Institute of Health grants (DK059579 to P.C.B. and DK098468 to A.V.M.), the NIH National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR001881 (to D.E.), the Larry L. Hillblom Foundation (2014-D-001-NET) (to P.C.B.), Translational Imaging Center, Leica Microsystems, the Bridge Institute at the USC Michelson Center for Convergent Bioscience, and the USC Office of the Provost. We acknowledge the technical assistance of Tristan Grogan, Department of Medicine Biostatistics Core at UCLA for help with data analysis. We would like to thank Patrick Rorsman University of Oxford and Jakob Knudsen University of Copenhagen and the members of the Pancreatic Beta Cell Consortium at USC for their inspiring discussions and feedback. We acknowledge the excellent editorial assistance of Jessica Garcia. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s42003-021-02113-1",
language = "English (US)",
volume = "4",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Springer Nature",
number = "1",
}