title: Long-term culture and functionality of pancreatic islets monitored using microelectrode arrays.
abstract: 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.
authors.affiliation: NMI Natural and Medical Sciences Institute at the University of Tübingen, Department of Electrophysiology, Markwiesenstraße 55, D-72770 Reutlingen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Schönecker
authors.forename: Udo
authors.initials: U
authors.lastname: Kraushaar
authors.forename: Martina
authors.initials: M
authors.lastname: Düfer
authors.forename: Anika
authors.initials: A
authors.lastname: Sahr
authors.forename: Carmen
authors.initials: C
authors.lastname: Härdtner
authors.forename: Elke
authors.initials: E
authors.lastname: Guenther
authors.forename: Reinhard
authors.initials: R
authors.lastname: Walther
authors.forename: Uwe
authors.initials: U
authors.lastname: Lendeckel
authors.forename: Winfried
authors.initials: W
authors.lastname: Barthlen
authors.forename: Peter
authors.initials: P
authors.lastname: Krippeit-Drews
authors.forename: Gisela
authors.initials: G
authors.lastname: Drews
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000379:methods; D005947:Glucose / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D018384:Oxidative Stress / Q000502:physiology*; D013113:Spin Labels
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D006861:Hydrogen Peroxide; D005947:Glucose; C001803:tempol