title: Oscillatory glucose flux in INS 1 pancreatic β cells: a self-referencing microbiosensor study.
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.
authors.affiliation: Physiological Sensing Facility, 1203 W. State Street, Purdue University, West Lafayette, IN 47907-2057, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Shi
authors.forename: Eric S
authors.initials: ES
authors.lastname: McLamore
authors.forename: David
authors.initials: D
authors.lastname: Jaroch
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Claussen
authors.forename: Raghavendra G
authors.initials: RG
authors.lastname: Mirmira
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Rickus
authors.forename: D Marshall
authors.initials: DM
authors.lastname: Porterfield
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007700:Kinetics; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats
chemical_list: C498776:GLUT6 protein, rat; D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; C495683:Slc2a2 protein, rat; D005947:Glucose; D010100:Oxygen; D002118:Calcium