Metabolic Oscillations in Pancreatic Islets Depend on the Intracellular Ca2+ Level but Not Ca2+ Oscillations

Authors

Matthew J. Merrins, University of Michigan - Ann Arbor
Bernard Fendler, Florida State University
Min Zhang, Virginia Commonwealth University
Arthur Sherman, National Institutes of Health
Richard Bertram, Florida State University
Leslie S. Satin, University of Michigan - Ann Arbor

Document Type

Article

Original Publication Date

2010

Journal/Book/Conference Title

The Biophysical Journal

Volume

99

Issue

1

First Page

76

Last Page

84

DOI of Original Publication

10.1016/j.bpj.2010.04.012

Comments

Originally published at http://dx.doi.org/10.1016/j.bpj.2010.04.012

Under an Elsevier user license.

Date of Submission

February 2015

Abstract

Abstract

Plasma insulin is pulsatile and reflects oscillatory insulin secretion from pancreatic islets. Although both islet Ca²⁺ and metabolism oscillate, there is disagreement over their interrelationship, and whether they can be dissociated. In some models of islet oscillations, Ca²⁺ must oscillate for metabolic oscillations to occur, whereas in others metabolic oscillations can occur without Ca²⁺ oscillations. We used NAD(P)H fluorescence to assay oscillatory metabolism in mouse islets stimulated by 11.1 mM glucose. After abolishing Ca²⁺ oscillations with 200 μM diazoxide, we observed that oscillations in NAD(P)H persisted in 34% of islets (n = 101). In the remainder of the islets (66%) both Ca²⁺ and NAD(P)H oscillations were eliminated by diazoxide. However, in most of these islets NAD(P)H oscillations could be restored and amplified by raising extracellular KCl, which elevated the intracellular Ca²⁺ level but did not restore Ca²⁺oscillations. Comparatively, we examined islets from ATP-sensitive K⁺ (K_ATP) channel-deficient SUR1^−/−mice. Again NAD(P)H oscillations were evident even though Ca²⁺ and membrane potential oscillations were abolished. These observations are predicted by the dual oscillator model, in which intrinsic metabolic oscillations and Ca²⁺ feedback both contribute to the oscillatory islet behavior, but argue against other models that depend on Ca²⁺ oscillations for metabolic oscillations to occur.

Rights

From The Biophysical Journal, Merrins, M.J., Fendler, B., Zhang, M., et al., Metabolic Oscillations in Pancreatic Islets Depend on the Intracellular Ca2+ Level but Not Ca2+ Oscillations, Vol. 99, Page 76. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. Reprinted with permission.

Is Part Of

VCU Pharmacology and Toxicology Publications