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

doi:10.1016/j.isci.2021.103250

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

iScience. 2021 Oct 9;24(11):103250. doi: 10.1016/j.isci.2021.103250. eCollection 2021 Nov 19.

Authors

Marianne Böni-Schnetzler^{1

2}, Hélène Méreau^{1

2}, Leila Rachid^{1

2}, Sophia J Wiedemann^{1

2}, Friederike Schulze^{1

2}, Kelly Trimigliozzi^{1

2}, Daniel T Meier^{1

2}, Marc Y Donath^{1

2}

Affiliations

¹ Endocrinology, Diabetes, and Metabolism, University Hospital of Basel, 4031 Basel, Switzerland.
² Department of Biomedicine, Diabetes Research, University of Basel, 4031 Basel, Switzerland.

Abstract

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.

Keywords: Cell biology; Cellular physiology; Physiology.