PMID- 24658612 OWN - NLM STAT- MEDLINE DCOM- 20141208 LR - 20151119 IS - 1757-9708 (Electronic) IS - 1757-9694 (Linking) VI - 6 IP - 5 DP - 2014 May TI - Long-term culture and functionality of pancreatic islets monitored using microelectrode arrays. PG - 540-4 LID - 10.1039/c3ib40261d [doi] AB - 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 long-term 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. FAU - Schonecker, Sven AU - Schonecker S AD - NMI Natural and Medical Sciences Institute at the University of Tubingen, Department of Electrophysiology, Markwiesenstrasse 55, D-72770 Reutlingen, Germany. FAU - Kraushaar, Udo AU - Kraushaar U FAU - Dufer, Martina AU - Dufer M FAU - Sahr, Anika AU - Sahr A FAU - Hardtner, Carmen AU - Hardtner C FAU - Guenther, Elke AU - Guenther E FAU - Walther, Reinhard AU - Walther R FAU - Lendeckel, Uwe AU - Lendeckel U FAU - Barthlen, Winfried AU - Barthlen W FAU - Krippeit-Drews, Peter AU - Krippeit-Drews P FAU - Drews, Gisela AU - Drews G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Integr Biol (Camb) JT - Integrative biology : quantitative biosciences from nano to macro JID - 101478378 RN - 0 (Antioxidants) RN - 0 (Cyclic N-Oxides) RN - 0 (Spin Labels) RN - BBX060AN9V (Hydrogen Peroxide) RN - IY9XDZ35W2 (Glucose) RN - U78ZX2F65X (tempol) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Cyclic N-Oxides/pharmacology MH - Diabetes Mellitus, Type 2/*metabolism MH - Dose-Response Relationship, Drug MH - Electrophysiology/methods MH - Glucose/*pharmacology MH - Hydrogen Peroxide/antagonists & inhibitors/metabolism MH - Islets of Langerhans/*metabolism MH - Membrane Potentials/*physiology MH - Mice, Inbred C57BL MH - Microelectrodes MH - Oxidative Stress/*physiology MH - Spin Labels EDAT- 2014/03/25 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/03/25 06:00 PHST- 2014/03/25 06:00 [entrez] PHST- 2014/03/25 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - 10.1039/c3ib40261d [doi] PST - ppublish SO - Integr Biol (Camb). 2014 May;6(5):540-4. doi: 10.1039/c3ib40261d.