Microfluidic glucose stimulation reveals limited coordination of intracellular Ca2+ activity oscillations in pancreatic islets

Jonathan V. Rocheleau, Glenn M. Walker, Steven S. Head, Owen P. McGuinness, David W. Piston

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

The pancreatic islet is a functional microorgan involved in maintaining normoglycemia through regulated secretion of insulin and other hormones. Extracellular glucose stimulates insulin secretion from islet β cells through an increase in redox state, which can be measured by NAD(P)H autofluorescence. Glucose concentrations over ∼7 mM generate synchronous oscillations in β cell intracellular Ca2+ concentration ([Ca2+]i), which lead to pulsatile insulin secretion. Prevailing models assume that the pancreatic islet acts as a functional syncytium, and the whole islet [Ca2+]i response has been modeled in terms of islet bursting and pacemaker models. To test these models, we developed a microfluidic device capable of partially stimulating an islet, while allowing observation of the NAD(P)H and [Ca2+]i responses. We show that β cell [Ca2+]i oscillations occur only within regions stimulated with more than ∼6.6 mM glucose. Furthermore, we show that tolbutamide, an antagonist of the ATP-sensitive K + channel, allows these oscillations to travel farther into the nonstimulated regions of the islet. Our approach shows that the extent of Ca2+ propagation across the islet depends on a delicate interaction between the degree of coupling and the extent of ATP-sensitive K +-channel activation and illustrates an experimental paradigm that will have utility for many other biological systems.

Original languageEnglish
Pages (from-to)12899-12903
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number35
DOIs
StatePublished - Aug 31 2004
Externally publishedYes

Keywords

  • ATP-sensitive K channels NAD(P)H
  • β cell

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