Live-cell imaging of glucose-induced metabolic coupling of β and α cell metabolism in health and type 2 diabetes
Zhongying Wang, Tatyana Gurlo, Aleksey V. Matveyenko, David Elashoff, Peiyu Wang, Madeline Rosenberger, Jason A. Junge, Raymond C. Stevens, Kate L. White, Scott E. Fraser, Peter C. Butler
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.