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

Incretin
DOI: 10.7554/elife.88189.3 Publication Date: 2023-10-03T12:30:48Z
ABSTRACT
Insufficient insulin secretion to meet metabolic demand results in diabetes. The intracellular flux of Ca 2+ 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 glucose-dependent insulinotropic polypeptide (GIP); and (4) 2 glucose. These stimuli interrogate β-cell function, α- 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 single-nucleotide polymorphisms genome-wide association studies. 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, nominate novel regulators oscillations with potential relevance function. also provide resource identifying appropriate which study regulators.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (98)
CITATIONS (3)