Oscillatory glucose flux in INS 1 pancreatic β cells: A self-referencing microbiosensor study

Jin Shi, Eric S. McLamore, David Jaroch, Jonathan C. Claussen, Raghavendra G. Mirmira, Jenna L. Rickus, D. Marshall Porterfield

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Signaling and insulin secretion in β cells have been reported to demonstrate oscillatory modes, with abnormal oscillations associated with type 2 diabetes. We investigated cellular glucose influx in β cells with a self-referencing (SR) microbiosensor based on nanomaterials with enhanced performance. Dose-response analyses with glucose and metabolic inhibition studies were used to study oscillatory patterns and transporter kinetics. For the first time, we report a stable and regular oscillatory uptake of glucose (averaged period 2.9 ± 0.6 min), which corresponds well with an oscillator model. This oscillatory behavior is part of the feedback control pathway involving oxygen, cytosolic Ca 2+/ATP, and insulin secretion (periodicity approximately 3 min). Glucose stimulation experiments show that the net Michaelis-Menten constant (6.1 ± 1.5 mM) is in between GLUT2 and GLUT9. Phloretin inhibition experiments show an EC 50 value of 28 ± 1.6 μM phloretin for class I GLUT proteins and a concentration of 40 ± 0.6 μM phloretin caused maximum inhibition with residual nonoscillating flux, suggesting that the transporters not inhibited by phloretin are likely responsible for the remaining nonoscillatory uptake, and that impaired uptake via GLUT2 may be the cause of the oscillation loss in type 2 diabetes. Transporter studies using the SR microbiosensor will contribute to diabetes research and therapy development by exploring the nature of oscillatory transport mechanisms.

Original languageEnglish (US)
Pages (from-to)185-193
Number of pages9
JournalAnalytical biochemistry
Volume411
Issue number2
DOIs
StatePublished - Apr 15 2011

Keywords

  • β Cell
  • Biosensor
  • Diabetes
  • Glucose oxidase
  • Glycolysis
  • Self-referencing

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology
  • Cell Biology

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