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Phase Analysis of Metabolic Oscillations and Membrane Potential in Pancreatic Islet β-Cells.

Title: Phase Analysis of Metabolic Oscillations and Membrane Potential in Pancreatic Islet β-Cells.
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Name(s): Merrins, Matthew J, author
Poudel, Chetan, author
McKenna, Joseph P, author
Ha, Joon, author
Sherman, Arthur, author
Bertram, Richard, author
Satin, Leslie S, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2016-02-02
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Metabolism in islet β-cells displays oscillations that can trigger pulses of electrical activity and insulin secretion. There has been a decades-long debate among islet biologists about whether metabolic oscillations are intrinsic or occur in response to oscillations in intracellular Ca(2+) that result from bursting electrical activity. In this article, the dynamics of oscillatory metabolism were investigated using five different optical reporters. Reporter activity was measured simultaneously with membrane potential bursting to determine the phase relationships between the metabolic oscillations and electrical activity. Our experimental findings suggest that Ca(2+) entry into β-cells stimulates the rate of mitochondrial metabolism, accounting for the depletion of glycolytic intermediates during each oscillatory burst. We also performed Ca(2+) clamp tests in which we clamped membrane potential with the KATP channel-opener diazoxide and KCl to fix Ca(2+) at an elevated level. These tests confirm that metabolic oscillations do not require Ca(2+) oscillations, but show that Ca(2+) plays a larger role in shaping metabolic oscillations than previously suspected. A dynamical picture of the mechanisms of oscillations emerged that requires the restructuring of contemporary mathematical β-cell models, including our own dual oscillator model. In the companion article, we modified our model to account for these new data.
Identifier: FSU_pmch_26840733 (IID), 10.1016/j.bpj.2015.12.029 (DOI), PMC4744170 (PMCID), 26840733 (RID), 26840733 (EID), S0006-3495(15)04813-4 (PII)
Grant Number: K01-DK101683, R01 DK046409, K01 DK101683, , P30 DK020572
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744170.
Subject(s): Animals
Calcium Signaling
Cells, Cultured
Insulin-Secreting Cells/metabolism
Insulin-Secreting Cells/physiology
KATP Channels/metabolism
Membrane Potentials
Mice
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_26840733
Owner Institution: FSU
Is Part Of: Biophysical journal.
1542-0086
Issue: iss. 3, vol. 110

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Merrins, M. J., Poudel, C., McKenna, J. P., Ha, J., Sherman, A., Bertram, R., & Satin, L. S. (2016). Phase Analysis of Metabolic Oscillations and Membrane Potential in Pancreatic Islet β-Cells. Biophysical Journal. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_26840733