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Oscillatory glucose flux in INS 1 pancreatic beta cells: A self-referencing microbiosensor study
ANALYTICAL BIOCHEMISTRY
  • Jin Shi, Birck Nanotechnology Center, Bindley Bioscience Center, Purdue University
  • Eric McLamore, Birck Nanotechnology Center, Bindley Bioscience Center, Purdue University
  • David Jaroch, Birck Nanotechnology Center, Bindley Bioscience Center, Purdue University
  • Jonathan C. Claussen, Birck Nanotechnology Center, Bindley Bioscience Center, Purdue University
  • Raghavendra Mirmira, Indiana University-Purdue University Indianapolis
  • Jenna Rickus, Birck Nanotechnology Center, Bindley Bioscience Center, Purdue University
  • D. Marshall Porterfield, Birck Nanotechnology Center, Bindley Bioscience Center, Purdue University
Abstract
Signaling and insulin secretion in beta cells have been reported to demonstrate oscillatory modes, with abnormal oscillations associated with type 2 diabetes. We investigated cellular glucose influx in beta 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 mu M phloretin for class I GLUT proteins and a concentration of 40 +/- 0.6 mu M 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. (C) 2010 Elsevier Inc. All rights reserved.
Keywords
  • Glucose oxidase; Biosensor; Self-referencing; Diabetes; Glycolysis; beta Cell; PULSATILE INSULIN-SECRETION; CARBON NANOTUBES; OXYGEN-CONSUMPTION; FREE CA2+; METABOLIC OSCILLATIONS; FEEDBACK-CONTROL; ATP/ADP RATIO; ISLETS; BIOSENSOR; TRANSPORT
Date of this Version
4-15-2011
DOI
10.1016/j.ab.2010.12.019
Citation
Analytical Biochemistry Volume 411, Issue 2, 15 April 2011, Pages 185–193
Citation Information
Jin Shi, Eric McLamore, David Jaroch, Jonathan C. Claussen, et al.. "Oscillatory glucose flux in INS 1 pancreatic beta cells: A self-referencing microbiosensor study" ANALYTICAL BIOCHEMISTRY (2011)
Available at: http://works.bepress.com/jonathan_claussen/1/