EX VIVO INTERMITTENT HYPOXIA PRECONDITIONING OF PANCREATIC ISLETS FOR IMPROVED FUNCTION UNDER HYPOXIA

摘要

Simultaneous stimulation of ex vivo pancreatic islets with dynamic oxygen and glucose loads is critical to understand how hypoxia alters the glucose-insulin response, especially for transplant applications. Standard techniques using a hypoxic chamber cannot provide both modulations with real-time monitoring. Using microfluidics with integrated glucose and oxygen modulation, hypoxic impairment of islet responses was quantified in calcium response, mitochondrial potential, and insulin secretion. More importantly, hypoxic responses were improved by preconditioning islets with intermittent hypoxia (IH), translating to improved insulin secretion. In addition, blocking mitochondrial KATP channels removes benefits of IH, consistent with understood mechanisms in cardiac myocytes preconditioning.