Nature Communications (Feb 2022)
Beta-cell specific Insr deletion promotes insulin hypersecretion and improves glucose tolerance prior to global insulin resistance
- Søs Skovsø,
- Evgeniy Panzhinskiy,
- Jelena Kolic,
- Haoning Howard Cen,
- Derek A. Dionne,
- Xiao-Qing Dai,
- Rohit B. Sharma,
- Lynda Elghazi,
- Cara E. Ellis,
- Katharine Faulkner,
- Stephanie A. M. Marcil,
- Peter Overby,
- Nilou Noursadeghi,
- Daria Hutchinson,
- Xiaoke Hu,
- Hong Li,
- Honey Modi,
- Jennifer S. Wildi,
- J. Diego Botezelli,
- Hye Lim Noh,
- Sujin Suk,
- Brian Gablaski,
- Austin Bautista,
- Ryekjang Kim,
- Corentin Cras-Méneur,
- Stephane Flibotte,
- Sunita Sinha,
- Dan S. Luciani,
- Corey Nislow,
- Elizabeth J. Rideout,
- Eric N. Cytrynbaum,
- Jason K. Kim,
- Ernesto Bernal-Mizrachi,
- Laura C. Alonso,
- Patrick E. MacDonald,
- James D. Johnson
Affiliations
- Søs Skovsø
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Evgeniy Panzhinskiy
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Jelena Kolic
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Haoning Howard Cen
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Derek A. Dionne
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Xiao-Qing Dai
- Alberta Diabetes Institute and Department of Pharmacology, University of Alberta
- Rohit B. Sharma
- Division of Endocrinology, Diabetes and Metabolism and the Weill Center for Metabolic Health, Weill Cornell Medicine
- Lynda Elghazi
- Department of Ophthalmology and Visual Sciences, University of Michigan Kellogg Eye Center
- Cara E. Ellis
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Katharine Faulkner
- Department of Mathematics, University of British Columbia
- Stephanie A. M. Marcil
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Peter Overby
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Nilou Noursadeghi
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Daria Hutchinson
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Xiaoke Hu
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Hong Li
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Honey Modi
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Jennifer S. Wildi
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- J. Diego Botezelli
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Hye Lim Noh
- Program in Molecular Medicine University of Massachusetts Medical School
- Sujin Suk
- Program in Molecular Medicine University of Massachusetts Medical School
- Brian Gablaski
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Massachusetts Medical School
- Austin Bautista
- Alberta Diabetes Institute and Department of Pharmacology, University of Alberta
- Ryekjang Kim
- Alberta Diabetes Institute and Department of Pharmacology, University of Alberta
- Corentin Cras-Méneur
- Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan
- Stephane Flibotte
- UBC Life Sciences Institute Bioinformatics Facility, University of British Columbia
- Sunita Sinha
- UBC Sequencing and Bioinformatics Consortium, Pharmaceutical Sciences, University of British Columbia
- Dan S. Luciani
- BC Children’s Hospital Research Institute, Department of Surgery, Faculty of Medicine, University of British Columbia
- Corey Nislow
- UBC Sequencing and Bioinformatics Consortium, Pharmaceutical Sciences, University of British Columbia
- Elizabeth J. Rideout
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- Eric N. Cytrynbaum
- Department of Mathematics, University of British Columbia
- Jason K. Kim
- Program in Molecular Medicine University of Massachusetts Medical School
- Ernesto Bernal-Mizrachi
- Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine and Miami VA Health Care System
- Laura C. Alonso
- Division of Endocrinology, Diabetes and Metabolism and the Weill Center for Metabolic Health, Weill Cornell Medicine
- Patrick E. MacDonald
- Alberta Diabetes Institute and Department of Pharmacology, University of Alberta
- James D. Johnson
- Diabetes Research Group, Life Sciences Institute, and Department of Cellular and Physiological Sciences, University of British Columbia
- DOI
- https://doi.org/10.1038/s41467-022-28039-8
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 22
Abstract
Insulin receptor protein is present in pancreatic β-cells, but the consequences of β-cell insulin resistance are incompletely understood. Here the authors use a combination of mouse studies and mathematical modelling to show that loss of beta-cell insulin receptor affects male and female mice differently and can contribute to hyperinsulinemia in the context of glucose stimulation.
