Dynamic Measurements of Oxygen Tension in Islets of Langerhans

Abstract

Oxidative metabolism plays a key role in glucose-induced insulin release (Ashcroft et al., 1973). With the development of a sensitive assay for insulin it was possible to characterize the dynamics of glucose-induced insulin release from the individual isolated islet of Langerhans (Bergsten and Hellman, 1993). To evaluate the role of the oxidative metabolism for the kinetics of insulin release a method for determining oxidative metabolism with a sensitivity comparable to that available for insulin is crucial. Glucose oxidation and oxygen consumption have been used to monitor glucose-induced metabolic changes (Ashcroft et al., 1973; Hutton and Malaisse, 1980; Longo et al., 1991). These studies indicate that insulin release and cellular metabolism, oxidation in particular, are tightly linked. However, the previously used techniques lack the sensitivity required to monitor the dynamics of metabolism from individual islets. Thus analysis of the coupling or synchronization between metabolic changes and secretion is hampered. To overcome this problem we have developed a new sensitive technique to monitor oxygen tension, which allows time-resolved measurements from individual islets, and characterized the responses in pO₂ following exposure to glycolytic and mitochondrial substrates.