Fig. 1.

Overlapping transcriptomic, metabolic and energy-sensing machinery that enables the functional maturation of beta cells. The ability of beta cells to derive GSIS is dependent on the synergistic interplay of many metabolic and regulatory features. The post-weaning maturation of beta cells is characterised by the re-balancing of the AMPK/mTOR energy-sensing pathways and their interaction with circadian clock entrainment. Both of these elements further interact with the canonical triggering and metabolic amplification pathways of GSIS involving NADP-mediated glutathione redox cycling. The feedback between these metabolic and nutrient-sensitive control points also trigger/respond to transcriptional shifts of maturation-associated genes, microRNA regulation and epigenetic signatures in beta cells. Dotted arrows with ‘?’ symbols denote indirect or mechanistically unknown pathways of regulation. GSH, glutathione; S-AMP, adenylosuccinate. This figure is available as part of a downloadable slideset