Stimulus/Secretion Coupling Factors in Glucose-Stimulated Insulin Secretion
Insights Gained From a Multidisciplinary Approach
- Christopher B. Newgard1,
- Danhong Lu1,
- Mette Valentin Jensen1,
- Jonathan Schissler1,
- Anne Boucher1,
- Shawn Burgess2 and
- A. Dean Sherry2
- 1Sarah W. Stedman Center for Nutritional Studies, Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina
- 2Department of Radiology and Rogers NMR Center, University of Texas Southwestern Medical Center, Dallas, Texas
Abstract
There is a growing appreciation for the complexity of the pathways involved in glucose-stimulated insulin secretion (GSIS) from pancreatic islet β-cells. In our laboratory, this has stimulated the development of an interdisciplinary approach to the problem. In this study, we review recent studies combining the tools of recombinant adenovirus for gene delivery, the development of novel cell lines that exhibit either robust or weak GSIS, and nuclear magnetic resonance imaging for metabolic fingerprinting of glucose-stimulated cells. Using these tools, we demonstrate a potentially important role for pyruvate carboxylase−mediated pyruvate cycling pathways in the control of GSIS, and discuss potential coupling factors produced by such pathways.
Footnotes
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Address correspondence and reprint requests to Christopher B. Newgard, Department of Pharmacology & Cancer Biology, DUMC 3813, Durham, NC 27710. E-mail: newga002{at}mc.duke.edu.
Received for publication 20 March 2002 and accepted in revised form 8 May 2002.
DMM, dimethylmalate; GSIS, glucose-stimulated insulin secretion; KATP channel, ATP-sensitive potassium channel; MCD, malonyl-CoA decarboxylase; NMR, nuclear magnetic resonance; PAA, phenylacetic acid; PC, pyruvate carboxylase; PDH, pyruvate dehydrogenase complex; TCA, tricarboxylic acid.
The symposium and the publication of this article have been made possible by an unrestricted educational grant from Servier, Paris.
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