Long-term culture and functionality of pancreatic islets monitored using microelectrode arrays

Extracellular recording of the glucose-induced electrical activity of mouse islets of Langerhans on microelectrode arrays (MEAs) is an innovative and powerful tool to address beta-cell (patho-) physiology. In a dual approach we tested whether this technique can detect concentration-dependent drug effects as well as characterize alterations in beta-cell activity during prolonged culture. First we established conditions that allow long-term investigation of beta-cell function by recording electrical activity. The results provide the first measurements of beta-cell membrane potential oscillations of individual murine islets during longterm culture. Oscillations were recorded for up to 34 days after islet isolation. Importantly, the glucose dependence of electrical activity did not change over a period of one month. Thus we can follow electrophysiological changes of individual islets induced by alterations in the beta-cell environment over weeks. Second, we used the MEA technique to assay beta-cell damage induced by oxidative stress and to evaluate appropriate protection mechanisms. Oxidative stress plays a key role in the development of type 2 diabetes mellitus (T2DM). Examination of the acute effects of H2O2 on electrical activity showed that the oxidant reduced the electrical activity in a concentration-dependent manner. The superoxide dismutase mimetic, tempol, protected against the detrimental effects of H2O2. In conclusion, we demonstrated that MEA recordings can be used to address disease-related mechanisms and protective interventions in beta-cells. In the future, this fundamental work should enable the monitoring of the electrical activity of islets of Langerhans under controlled ex vivo conditions including long-term exposure to oxidative stress, glucolipotoxicity, and other diabetes-inducing agents.