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Insulin Secretion from Pancreatic Beta Cells (complete)


PROJECT INVESTIGATORS

Emma Heart, PhD
BioCurrents Research Center

Barbara Corkey, PhD
Boston University Medical Center

Peter J.S. Smith, PhD
Director & Sr. Scientist
BioCurrents Research Center


E. Heart
Description:

Reducing equivalents, NADPH and NADH play an important role in regulation of insulin secretion from pancreatic islet cells. Both cytosolic and mitochondrial metabolism, and resulting changes in reducing equivalents in both pools, are important factors in this process.

Packaging and secretion of insulin
Packaging and secretion of insulin from a pancreatic beta cell.

To further elucidate the roles of cytosolic and mitochondrial components, we have been studying NAD(P)H responses of whole mouse and rat pancreatic islets to insulin secretagogues, glucose and the exclusive mitochondrial substrate succinate, using Zeiss LSM confocal microscope equipped with 2-photon laser which we have used for excitation of NAD(P)H. We were able to collect data showing differential effects of the mitochondrial fuel succinate on NAD(P)H levels in the rat and mouse, which have different degrees of cytosolic versus mitochondrial metabolism. This work will help in understanding the molecular mechanism underlying insulin secretion to different insulin secretagogues, and ultimately impairment of insulin release if this function is in the type 2 diabetic conditions. This work was done as a part of Dr. Heart's Grass Fellowship at the BioCurrents Research Center where she is now Research Assistant Scientist .

Selected Publications:

Heart, E., Corkey, R.F., Wikstrom, J.D., Shirihai, O.S. and Corkey, B.F. 2006. Glucose-dependent increase in mitochondrial membrane potential, but not cytoplasmic calcium, correlates with insulin secretion in single islet cells. American Journal of Physiology. Endocrinology & Metabolism. 290 (1) : E143- E148.

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