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Postnatal maturation of calcium signaling in islets of Langerhans from neonatal mice


West HL , Corbin KL , D'Angelo CV , Donovan LM , Jahan I , Gu G , Nunemaker CS , . Cell calcium. 2020 12 28; 94(). 102339


Pancreatic islet cells develop mature physiological responses to glucose and other fuels postnatally. In this study, we used fluorescence imaging techniques to measure changes in intracellular calcium ([Ca]) to compare islets isolated from mice on postnatal days 0, 4, and 12 with islets from adult CD-1 mice. In addition, we used publicly available RNA-sequencing data to compare expression levels of key genes in β-cell physiology with [Ca] data across these ages. We show that islets isolated from mice on postnatal day 0 displayed elevated [Ca] in basal glucose (≤4 mM) but lower [Ca] responses to stimulation by 12-20 mM glucose compared to adult. Neonatal islets displayed more adult-like [Ca] in basal glucose by day 4 but continued to show lower [Ca] responses to 16 and 20 mM glucose stimulation up to at least day 12. A right shift in glucose sensing (EC) correlated with lower fragment-per-kilobase-of-transcript-per-million-reads-mapped (FPKM) of Slc2a2 (glut2) and Actn3 and increased FPKM for Galk1 and Nupr1. Differences in [Ca] responses to additional stimuli were also observed. Calcium levels in the endoplasmic reticulum were elevated on day 0 but became adult-like by day 4, which corresponded with reduced expression in Atp2a2 (SERCA2) and novel K+-channel Ktd17, increased expression of Pml, Wfs1, Thada, and Herpud1, and basal [Ca] maturing to adult levels. Ion-channel activity also matured rapidly, but RNA sequencing data mining did not yield strong leads. In conclusion, the maturation of islet [Ca] signaling is complex and multifaceted; several possible gene targets were identified that may participate in this process.