Insights into pancreatic β cell energy metabolism using rodent β cell models

Wellcome Open Research

article

Karl J Morten¹  Michelle Potter¹  Luned Badder¹  Pamela Sivathondan¹  Rebecca Dragovic¹  Abigale Neumann¹  James Gavin¹  Roshan Shrestha¹  Svetlana Reilly²  Kanchan Phadwal³  Tiffany A. Lodge¹  Angela Borzychowski¹  Sharon Cookson⁴  Corey Mitchell¹  Alireza Morovat⁵  Anna Katharina Simon⁶  Johanna Uusimaa⁷  James Hynes⁸  Joanna Poulton¹ 

[1] Nuffield Department of Obstetrics & Gynaecology, The Women’s Centre, University of Oxford, John Radcliffe Hospital;Department of Cardiovascular Medicine, John Radcliffe Hospital;BRC Translational Immunology Lab, NIHR, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital;Institute of Cellular Medicine, Haematological Sciences, Medical School, Newcastle University;Clinical Biochemistry, John Radcliffe Hospital;Kennedy Institute of Rheumatology, University of Oxford;Department of Paediatrics, University of Oulu;Luxcel BioSciences Ltd, BioInnovation Centre, University College Cork

关键词: beta-cell;    oxidative phosphorylation;    reactive oxygen species;    superoxide;    mitochondria;    insulin secretion;   

DOI  :  10.12688/wellcomeopenres.10535.3

学科分类：内科医学

来源: Wellcome

【 摘 要 】

Background: Mitochondrial diabetes is primarily caused by β-cell failure, a cell type whose unique properties are important in pathogenesis.Methods: By reducing glucose, we induced energetic stress in two rodent β-cell models to assess effects on cellular function.Results: Culturing rat insulin-secreting INS-1 cells in low glucose conditions caused a rapid reduction in whole cell respiration, associated with elevated mitochondrial reactive oxygen species production, and an altered glucose-stimulated insulin secretion profile. Prolonged exposure to reduced glucose directly impaired mitochondrial function and reduced autophagy.Conclusions: Insulinoma cell lines have a very different bioenergetic profile to many other cell lines and provide a useful model of mechanisms affecting β-cell mitochondrial function.

【 授权许可】

CC BY