Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Effect of cAMP and the Role of Epac2A During Activation, Activity, and Deactivation of Beta Cell Networks

Version 1 : Received: 30 April 2021 / Approved: 5 May 2021 / Online: 5 May 2021 (13:34:10 CEST)

How to cite: Skelin Klemen, M.; Dolenšek, J.; Križančić Bombek, L.; Pohorec, V.; Gosak, M.; Slak Rupnik, M.; Stožer, A. The Effect of cAMP and the Role of Epac2A During Activation, Activity, and Deactivation of Beta Cell Networks. Preprints 2021, 2021050064 (doi: 10.20944/preprints202105.0064.v1). Skelin Klemen, M.; Dolenšek, J.; Križančić Bombek, L.; Pohorec, V.; Gosak, M.; Slak Rupnik, M.; Stožer, A. The Effect of cAMP and the Role of Epac2A During Activation, Activity, and Deactivation of Beta Cell Networks. Preprints 2021, 2021050064 (doi: 10.20944/preprints202105.0064.v1).

Abstract

Beta cells couple stimulation by glucose with insulin secretion and impairments in this coupling play a central role in diabetes mellitus. To clarify the effect of cAMP and the role of Epac2A in intracellular calcium signals and intercellular coupling, we performed functional multicellular calcium imaging in beta cells in mouse pancreas tissue slices after stimulation with glucose and forskolin in wild-type and Epac2A knock-out mice. Increased cAMP evoked calcium signals in otherwise sub-stimulatory glucose and beta cells from Epac2A knock-out mice displayed a faster activation. During the plateau phase, beta cells from Epac2A knock-out mice displayed a slightly higher active time in response to glucose compared with wild-type littermates, and increased cAMP increased the active time via a large increase in oscillation frequency and small decrease in oscillation duration in both Epac2A knock-out and wild-type mice. Functional network properties during stimulation with glucose did not differ in Epac2A knock-out mice, but the presence of Epac2A was crucial for the protective effect of increased cAMP in preventing a decline in beta cell functional connectivity with time. Finally, increased cAMP prolonged beta cell activity during deactivation in an Epac2A-independent manner.

Subject Areas

pancreas; tissue slices; beta cells; calcium imaging; amplifying pathway; forskolin; Epac2A KO

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