Novel regulators of islet function identified from genetic variation in mouse islet Ca2+ oscillations

• DOI: 10.7554/elife.88189.1
• Publication Date: 2023-06-13T12:17:19Z
• Authors: Christopher H. Em...; Lauren E. Clark; Brian Yandell; Kathryn L. Schueler; Shane P. Simonett; Donnie S. Stapleton; Kelly A. Mitok; Matthew J. Merrins; Mark P. Keller; Alan D. Attie
• Keywords: Variation (astronomy)

Abstract Insufficient insulin secretion to meet metabolic demand results in diabetes. The intracellular flux of Ca2+ into β-cells triggers release. Since genetics strongly influences variation islet secretory responses, we surveyed dynamics eight genetically diverse mouse strains. We found high strain response four conditions: 1) 8 mM glucose; 2) glucose plus amino acids; 3) glucose, acids, 10 nM GIP; and 4) 2 glucose. These stimuli interrogate β-cell function, α-cell signaling, incretin responses. then correlated components the waveforms protein abundances same strains used for measurements. To focus on proteins relevant human identified orthologues that are proximal glycemic-associated SNPs GWAS. Several have previously been shown regulate (e.g. ABCC8, PCSK1, GCK), supporting our mouse-to-human integration as a discovery platform. By integrating these data, nominated novel regulators oscillations with potential relevance function. also provide resource identifying appropriate which study regulators.