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

doi:10.1038/s42003-021-02113-1

Live-cell imaging of glucose-induced metabolic coupling of β and α cell metabolism in health and type 2 diabetes

Commun Biol. 2021 May 19;4(1):594. doi: 10.1038/s42003-021-02113-1.

Authors

Zhongying Wang^{1

2}, Tatyana Gurlo², Aleksey V Matveyenko³, David Elashoff⁴, Peiyu Wang^{1

5

6}, Madeline Rosenberger², Jason A Junge^{1

5}, Raymond C Stevens⁷, Kate L White¹, Scott E Fraser^{8

9

10}, Peter C Butler¹¹

Affiliations

¹ Department of Biological Sciences, Bridge Institute, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, USA.
² Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
³ Department of Medicine, Division of Endocrinology, Metabolism, Diabetes, and Nutrition, Mayo Clinic School of Medicine, Rochester, MN, USA.
⁴ Department of Biostatistics, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA.
⁵ Translational Imaging Center, University of Southern California, Los Angeles, CA, USA.
⁶ Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.
⁷ Department of Biological Sciences, Bridge Institute, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, USA. stevens@usc.edu.
⁸ Department of Biological Sciences, Bridge Institute, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, USA. sfraser@usc.edu.
⁹ Translational Imaging Center, University of Southern California, Los Angeles, CA, USA. sfraser@usc.edu.
¹⁰ Biomedical Engineering, University of Southern California, Los Angeles, CA, USA. sfraser@usc.edu.
¹¹ Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. pbutler@mednet.ucla.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus, Experimental / drug therapy
Diabetes Mellitus, Experimental / metabolism*
Diabetes Mellitus, Experimental / pathology
Diabetes Mellitus, Type 2 / drug therapy
Diabetes Mellitus, Type 2 / metabolism*
Diabetes Mellitus, Type 2 / pathology
Glucagon-Secreting Cells / drug effects
Glucagon-Secreting Cells / metabolism*
Glucose / pharmacology*
Glycolysis
Humans
Insulin-Secreting Cells / drug effects
Insulin-Secreting Cells / metabolism*
Islet Amyloid Polypeptide / metabolism
Male
Mice
Microscopy, Fluorescence
Molecular Imaging / methods*
Oxidative Phosphorylation
Rats
Rats, Sprague-Dawley
Rats, Transgenic

Substances

Islet Amyloid Polypeptide
Glucose

Abstract

Publication types

MeSH terms

Substances

Grants and funding