Modulation of large dense core vesicle insulin content mediates rhythmic hormone release from pancreatic beta cells over the 24h cycle - Université de Bourgogne Accéder directement au contenu
Article Dans Une Revue PLoS ONE Année : 2018

Modulation of large dense core vesicle insulin content mediates rhythmic hormone release from pancreatic beta cells over the 24h cycle

Résumé

The rhythmic nature of insulin secretion over the 24h cycle in pancreatic islets has been mostly investigated using transcriptomics studies showing that modulation of insulin secretion over this cycle is achieved via distal stages of insulin secretion. We set out to measure β-cell exocytosis using in depth cell physiology techniques at several time points. In agreement with the activity and feeding pattern of nocturnal rodents, we find that C57/Bl6J islets in culture for 24h exhibit higher insulin secretion during the corresponding dark phase than in the light phase (Zeitgeber Time ZT20 and ZT8, respectively, in vivo). Glucose-induced insulin secretion is increased by 21% despite normal intracellular Ca2+ transients 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 analyses show that vesicle size and density are unaltered, demonstrating that intravesicular insulin content per granule is modulated over the 24h cycle. Proinsulin levels did not change between ZT8 and ZT20. Islet glucagon content was inversely proportional to insulin content indicating that this unique feature is likely to support a physiological role. Microarray data identified the differential expression of 301 transcripts, of which 26 are miRNAs and 54 are known genes (including C2cd4b, a gene previously involved in insulin processing, and clock genes such as Bmal1 and Rev-erbα). Mouse β-cell secretion over the full course of the 24h cycle may rely on several distinct cellular functions but late night increase in insulin secretion depends solely on granule insulin content.
Fichier principal
Vignette du fichier
journal.pone.0193882.pdf (2.14 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-02331141 , version 1 (07-11-2019)

Licence

Paternité

Identifiants

Citer

Aurore Quinault, Corinne Leloup, Geoffrey Denwood, Coralie Spiegelhalter, Marianne Rodriguez, et al.. Modulation of large dense core vesicle insulin content mediates rhythmic hormone release from pancreatic beta cells over the 24h cycle. PLoS ONE, 2018, 13 (3), pp.e0193882. ⟨10.1371/journal.pone.0193882⟩. ⟨hal-02331141⟩
42 Consultations
32 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More