Stimulus/secretion coupling factors in glucose-stimulated insulin secretion: insights gained from a multidisciplinary approach.
There is a growing appreciation for the complexity of the pathways involved in glucose-stimulated insulin secretion (GSIS) from pancreatic islet beta-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.
Newgard
Christopher B
CB
Sarah W. Stedman Center for Nutritional Studies, Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. newga002@mc.duke.edu
Lu
Danhong
D
Jensen
Mette Valentin
MV
Schissler
Jonathan
J
Boucher
Anne
A
Burgess
Shawn
S
Sherry
A Dean
AD
D000818:Animals; D002460:Cell Line; D018014:Gene Transfer Techniques; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy
D007328:Insulin; D005947:Glucose