title: Islet preconditioning via multimodal microfluidic modulation of intermittent hypoxia.
abstract: Simultaneous stimulation of ex vivo pancreatic islets with dynamic oxygen and glucose is a critical technique for studying how hypoxia alters glucose-stimulated response, especially in transplant environments. Standard techniques using a hypoxic chamber cannot provide both oxygen and glucose modulations, while monitoring stimulus-secretion coupling factors in real-time. Using novel microfluidic device with integrated glucose and oxygen modulations, we quantified hypoxic impairment of islet response by calcium influx, mitochondrial potentials, and insulin secretion. Glucose-induced calcium response magnitude and phase were suppressed by hypoxia, while mitochondrial hyperpolarization and insulin secretion decreased in coordination. More importantly, hypoxic response was improved by preconditioning islets to intermittent hypoxia (IH, 1 min/1 min 5-21% cycling for 1 h), translating to improved insulin secretion. Moreover, blocking mitochondrial K(ATP) channels removed preconditioning benefits of IH, similar to mechanisms in preconditioned cardiomyocytes. Additionally, the multimodal device can be applied to a variety of dynamic oxygen-metabolic studies in other ex vivo tissues.
authors.affiliation: Department of Bioengineering, University of Illinois, Chicago, Illinois 60607, USA.
authors.forename: Joe F
authors.initials: JF
authors.lastname: Lo
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Alexander
authors.initials: A
authors.lastname: Blake
authors.forename: Gene
authors.initials: G
authors.lastname: Yu
authors.forename: Tricia A
authors.initials: TA
authors.lastname: Harvat
authors.forename: Hyojin
authors.initials: H
authors.lastname: Jeon
authors.forename: Jose
authors.initials: J
authors.lastname: Oberholzer
authors.forename: David T
authors.initials: DT
authors.lastname: Eddington
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000494:pharmacology*; D000860:Hypoxia; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D044085:Microfluidics; D008928:Mitochondria / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D019172:Transplantation Conditioning
chemical_list: D007328:Insulin; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D005947:Glucose; D010100:Oxygen; D002118:Calcium