Pancreas-derived DPP4 is not essential for glucose homeostasis under metabolic stress

Evgenia Fadzeyeva; Cassandra A.A. Locatelli; Natasha A. Trzaskalski; My-Anh Nguyen; Megan E. Capozzi; Branka Vulesevic; Nadya M. Morrow; Peyman Ghorbani; Antonio A. Hanson; Ilka Lorenzen-Schmidt; Mary-Anne Doyle; Richard Seymour; Elodie M. Varin; Morgan D. Fullerton; Jonathan E. Campbell; Erin E. Mulvihill

iScience (May 2023)

Pancreas-derived DPP4 is not essential for glucose homeostasis under metabolic stress

Evgenia Fadzeyeva,
Cassandra A.A. Locatelli,
Natasha A. Trzaskalski,
My-Anh Nguyen,
Megan E. Capozzi,
Branka Vulesevic,
Nadya M. Morrow,
Peyman Ghorbani,
Antonio A. Hanson,
Ilka Lorenzen-Schmidt,
Mary-Anne Doyle,
Richard Seymour,
Elodie M. Varin,
Morgan D. Fullerton,
Jonathan E. Campbell,
Erin E. Mulvihill

Affiliations

Evgenia Fadzeyeva: The University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, ON K1H 8M5, Canada; The University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
Cassandra A.A. Locatelli: The University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, ON K1H 8M5, Canada; The University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
Natasha A. Trzaskalski: The University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, ON K1H 8M5, Canada; The University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
My-Anh Nguyen: The University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, ON K1H 8M5, Canada; The University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
Megan E. Capozzi: Duke Molecular Physiology Institute, 300 North Duke Street, Durham, NC 27701, USA
Branka Vulesevic: The University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, ON K1H 8M5, Canada; The University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
Nadya M. Morrow: The University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, ON K1H 8M5, Canada; The University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
Peyman Ghorbani: The University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, ON K1H 8M5, Canada
Antonio A. Hanson: The University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, ON K1H 8M5, Canada; The University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
Ilka Lorenzen-Schmidt: The University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
Mary-Anne Doyle: Division of Endocrinology & Metabolism, Department of Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada
Richard Seymour: The University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
Elodie M. Varin: Lunenfeld Tanenbaum Research Institute, Toronto, ON M5G 1X5, Canada
Morgan D. Fullerton: The University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, ON K1H 8M5, Canada; Centre for Infection, Immunity and Inflammation, Ottawa, ON K1H 8M5, Canada
Jonathan E. Campbell: Duke Molecular Physiology Institute, 300 North Duke Street, Durham, NC 27701, USA
Erin E. Mulvihill: The University of Ottawa, Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, Ottawa, ON K1H 8M5, Canada; The University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada; Centre for Infection, Immunity and Inflammation, Ottawa, ON K1H 8M5, Canada; Montreal Diabetes Research Group, Montreal, QC H2X 0A9, Canada; Corresponding author

Journal volume & issue: Vol. 26, no. 5
p. 106748

Abstract

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Summary: Mice systemically lacking dipeptidyl peptidase-4 (DPP4) have improved islet health, glucoregulation, and reduced obesity with high-fat diet (HFD) feeding compared to wild-type mice. Some, but not all, of this improvement can be linked to the loss of DPP4 in endothelial cells (ECs), pointing to the contribution of non-EC types. The importance of intra-islet signaling mediated by α to β cell communication is becoming increasingly clear; thus, our objective was to determine if β cell DPP4 regulates insulin secretion and glucose tolerance in HFD-fed mice by regulating the local concentrations of insulinotropic peptides. Using β cell double incretin receptor knockout mice, β cell- and pancreas-specific Dpp4−/− mice, we reveal that β cell incretin receptors are necessary for DPP4 inhibitor effects. However, although β cell DPP4 modestly contributes to high glucose (16.7 mM)-stimulated insulin secretion in isolated islets, it does not regulate whole-body glucose homeostasis.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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