Transcriptomics

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Gene expression profiles from mouse pancreatic islets at ZT8 or ZT20


ABSTRACT: Expression studies in several models of type 2 Diabetes have suggested that exocytosis contributes to the modulation of insulin secretion during the 24h cycle. In agreement with the activity and feeding pattern of nocturnal rodents, we find that C57/Bl6J mice exhibit higher insulin secretion during the dark phase (ZT20 vs ZT8). Glucose-induced insulin secretion is increased by 21% despite normal intracellular Ca2+ signaling and depolarization-evoked exocytosis as measured by whole-cell capacitance measurements. This paradox is explained by a 1.37-fold increase in beta cell insulin content. Ultramorphological analysis show that vesicle size and density are unaltered but the intravesicular content per granule is modulated during the circadian rhythm. Proinsulin levels were not statistically different between the two time points despite a trend for reduction at ZT20. Islet glucagon content was inversely proportional to insulin content. Microarray data identified the differential expression of 301 transcripts of which, 54 known genes and 26 miRNA, including clock genes such as Bmal1 and Rev-erb . Differential expression of C2cd4b may contribute to the modulation of insulin content. Mice -cell secretion during the 24h cycle may rely on several distinct cellular functions but late night increase in insulin secretion depends solely on granule insulin content. A total of 301 genes were differentially expressed between ZT8 vs ZT20 islets . A majority were upregulated (199 between 1.3 to 2.71 fold) whilst 102 were down-regulated (<-1.3 fold). Given the focus of our study, current literature and our own results, genes involved in exocytosis, insulin production and of course, circadian rhythms were particularly interesting.

ORGANISM(S): Mus musculus

PROVIDER: GSE109882 | GEO | 2018/01/31

REPOSITORIES: GEO

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