IL-1beta promotes the age-associated decline of beta cell function

Marianne Böni-Schnetzler; Hélène Méreau; Leila Rachid; Sophia J. Wiedemann; Friederike Schulze; Kelly Trimigliozzi; Daniel T. Meier; Marc Y. Donath

iScience (Nov 2021)

IL-1beta promotes the age-associated decline of beta cell function

Marianne Böni-Schnetzler,
Hélène Méreau,
Leila Rachid,
Sophia J. Wiedemann,
Friederike Schulze,
Kelly Trimigliozzi,
Daniel T. Meier,
Marc Y. Donath

Affiliations

Marianne Böni-Schnetzler: Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, 4031 Basel, Switzerland; Department of Biomedicine, Diabetes Research, University of Basel, 4031 Basel, Switzerland; Corresponding author
Hélène Méreau: Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, 4031 Basel, Switzerland; Department of Biomedicine, Diabetes Research, University of Basel, 4031 Basel, Switzerland
Leila Rachid: Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, 4031 Basel, Switzerland; Department of Biomedicine, Diabetes Research, University of Basel, 4031 Basel, Switzerland
Sophia J. Wiedemann: Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, 4031 Basel, Switzerland; Department of Biomedicine, Diabetes Research, University of Basel, 4031 Basel, Switzerland
Friederike Schulze: Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, 4031 Basel, Switzerland; Department of Biomedicine, Diabetes Research, University of Basel, 4031 Basel, Switzerland
Kelly Trimigliozzi: Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, 4031 Basel, Switzerland; Department of Biomedicine, Diabetes Research, University of Basel, 4031 Basel, Switzerland
Daniel T. Meier: Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, 4031 Basel, Switzerland; Department of Biomedicine, Diabetes Research, University of Basel, 4031 Basel, Switzerland
Marc Y. Donath: Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, 4031 Basel, Switzerland; Department of Biomedicine, Diabetes Research, University of Basel, 4031 Basel, Switzerland

Journal volume & issue: Vol. 24, no. 11
p. 103250

Abstract

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Summary: Aging is the prime risk factor for the development of type 2 diabetes. We investigated the role of the interleukin-1 (IL-1) system on insulin secretion in aged mice. During aging, expression of the protective IL-1 receptor antagonist decreased in islets, whereas IL-1beta gene expression increased specifically in the CD45 + islet immune cell fraction. One-year-old mice with a whole-body knockout of IL-1beta had higher insulin secretion in vivo and in isolated islets, along with enhanced proliferation marker Ki67 and elevated size and number of islets. Myeloid cell-specific IL-1beta knockout preserved glucose-stimulated insulin secretion during aging, whereas it declined in control mice. Isolated islets from aged myeloIL-1beta ko mice secreted more insulin along with increased expression of Ins2, Kir6.2, and of the cell-cycle gene E2f1. IL-1beta treatment of isolated islets reduced E2f1, Ins2, and Kir6.2 expression in beta cells. We conclude that IL-1beta contributes the age-associated decline of beta cell function.

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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