Introduction: We recently showed that islets isolated from organs donated after medically assisted circulatory death (DCD V) have similar yield and survival compared to islets of DCD III origin. However, DCD V islets had a significantly lower insulin secretory response in vitro. We hypothesized that insulin secretory capacity is influenced by the use of the neuromuscular blocker rocuronium (a muscarinic receptor antagonist) that is applied in high dose before the DCD V procedure.

Method: Human EndoCBH1 beta cells were treated with rocuronium in gradually increasing concentrations mimicking levels in clinical practise. The treated cells were analysed for their changes regarding insulin secretory capacity, mitochondrial activity and ATP content in resting and stimulating glucose concentrations. Data are represented as changes compared to untreated cells.

Results: In comparison to untreated cells, rocuronium treatment lowered the stimulated insulin secretion index. At a concentration of 135 µM rocuronium, which is present during the DCD V procedure, there was a significant 24% reduction for the stimulated index compared to the untreated control (p=0.0008)(n=13). This reduction was due to a 35% increase in resting insulin secretion by rocuronium treatment (n=13; p=0.007) while during glucose stimulation comparable insulin concentrations were present. Resting mitochondrial activity was 15% increased at a concentration of 135 µM rocuronium (n=4; p=0.013) and 26% increased at a concentration of 180 µM rocuronium (n=4; p=0.055). During glucose stimulation mitochondrial activity was comparable to untreated cells. The ATP content increased by 23% in resting conditions at a rocuronium concentration of 135 µM (n=5; p=0.1) but remained unchanged during glucose stimulation.  

Conclusion: Rocuronium (in a concentration comparable to the use in DCD V procedures) altered the mitochondrial activity and insulin secretory pattern in beta cells especially during resting glucose conditions. Stimulated insulin secretion was unaffected by rocuronium. Further studies are needed to validate the underlying mechanism.