347-LB: MEA Technology as an Easy Electrophysiological Approach for Noninvasive Recordings of Intact Murine and Human Islets

Abstract

Increase of blood glucose concentration leads to glucose-induced electrical activity of pancreatic beta-cells followed by insulin secretion. Electrical activity appears in glucose concentration-dependent oscillations easily recorded by microelectrode arrays (MEA). In comparison to other electrophysiological techniques MEAs can record non-invasively from intact islets and can be used for long term studies to investigate chronic effects of drugs. Murine islets or islets isolated from human biopsies were used for recordings. Electrical activity was quantified as fraction of plateau Phase (FOPP) or number of single spike activity. Islets were placed via suction or cultivated on MEAs. The glucose concentration response curve recorded with murine islets plotted as FOPP revealed a half-maximal activity of 12 ± 2 mM which is in line with traditional methods like e.g., with intracellular electrodes. Glucose-induced activity of cultured islets remains stable over a month. Application of well-known substances (like e.g., diazoxide, tolbutamide) matched regular results. Human islets displayed typical glucose-induced activity (10 mM). Validation studies showed the existence of functional KATP channels and TTX reduced spike activity from 1047 ± 314 to 199 ± 90 spikes/5min after the application of 300 nM TTX. The washout led to an increased spike activity of 779 ± 301 spikes/minutes. The glucose concentration response curve revealed an EC50 value of 8 ± 3 mM glucose. The glucose responsiveness recorded with the MEA Technology is in line with other reports showing that the EC50 value of human beta-cells (∼ 6 mM) is lower than in mouse beta-cells. MEA Technology allows medium throughput recordings from up to 40 intact islets simultaneously. While previous electrophysiological attempts failed MEAs offer large scale research in both academics and industry. The principle of function is not limited to rodent but is also applicable to human or stem cell derived islets of Langerhans. Disclosure S. Schönecker: None. M. Oza: Employee; Self; Multichannel Systems, Gmbh. U. Kraushaar: None.