التفاصيل البيبلوغرافية
| العنوان: |
Novel regulators of islet function identified from genetic variation in mouse islet Ca2+ oscillations. |
| المؤلفون: |
Emfinger, Christopher H.1, Clark, Lauren E.1, Yandell, Brian2, Schueler, Kathryn L.1, Simonett, Shane P.1, Stapleton, Donnie S.1, Mitok, Kelly A.1, Merrins, Matthew J.3,4, Keller, Mark P.1, Attie, Alan D.1,3,5 adattie@wisc.edu |
| المصدر: |
eLife. 10/3/2023, p1-28. 28p. |
| مصطلحات موضوعية: |
*GENETIC variation, *ISLANDS, *GENOME-wide association studies, *INSULIN, *OSCILLATIONS, *MICE |
| مستخلص: |
Insufficient insulin secretion to meet metabolic demand results in diabetes. The intracellular flux of Ca2+ into β-cells triggers insulin release. Since genetics strongly influences variation in islet secretory responses, we surveyed islet Ca2+ dynamics in eight genetically diverse mouse strains. We found high strain variation in response to four conditions: (1) 8 mM glucose; (2) 8 mM glucose plus amino acids; (3) 8 mM glucose, amino acids, plus 10 nM glucose-dependent insulinotropic polypeptide (GIP); and (4) 2 mM glucose. These stimuli interrogate β-cell function, α-to β-cell signaling, and incretin responses. We then correlated components of the Ca2+ waveforms to islet protein abundances in the same strains used for the Ca2+ measurements. To focus on proteins relevant to human islet function, we identified human orthologues of correlated mouse proteins that are proximal to glycemic-associated single-nucleotide polymorphisms in human genome-wide association studies. Several orthologues have previously been shown to regulate insulin secretion (e.g. ABCC8, PCSK1, and GCK), supporting our mouse-to-human integration as a discovery platform. By integrating these data, we nominate novel regulators of islet Ca2+ oscillations and insulin secretion with potential relevance for human islet function. We also provide a resource for identifying appropriate mouse strains in which to study these regulators. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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