Islet preconditioning via multimodal microfluidic modulation of intermittent hypoxia

Anal Chem. 2012 Feb 21;84(4):1987-93. doi: 10.1021/ac2030909. Epub 2012 Feb 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Glucose / pharmacology*
  • Hypoxia*
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Microfluidics*
  • Mitochondria / drug effects
  • Oxygen / metabolism
  • Potassium Channels / metabolism
  • Transplantation Conditioning*


  • Insulin
  • Potassium Channels
  • mitochondrial K(ATP) channel
  • Glucose
  • Oxygen
  • Calcium