AMINO ACID NEUROTRANSMITTERS IN THE ENDOCRINE PANCREAS

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THIS IS A SHANNON AWARD PROVIDING PARTIAL SUPPORT FOR THE RESEARCH PROJECTS THAT FALL SHORT OF THE ASSIGNED INSTITUTE'S FUNDING RANGE BUT ARE IN THE MARGIN OF EXCELLENCE. THE SHANNON AWARD IS INTENDED TO PROVIDE SUPPORT TO TEST THE FEASIBILITY OF THE APPROACH; DEVELOP FURTHER TESTS AND REFINE RESEARCH TECHNIQUES; PERFORM SECONDARY ANALYSIS OR AVAILABLE DATA SETS; OR CONDUCT DISCRETE PROJECTS THAT CAN DEMONSTRATE THE PI'S RESEARCH CAPABILITIES OR LEND ADDITIONAL WEIGHT TO AN ALREADY MERITORIOUS APPLICATION. THE ABSTRACT BELOW IS TAKEN FROM THE ORIGINAL DOCUMENT SUBMITTED BY THE PRINCIPAL INVESTIGATOR. DESCRIPTION: (Applicant's abstract) To provide for better understanding of chemical signaling in the pancreatic islets of Langerhans, studies are proposed to examine the functional importance of amino acid neurotransmitters and their receptors in this tissue. Pancreatic islets appear to express receptors for the amino acid neurotransmitters GABA, glycine and glutamate, which subserve rapid synaptic communication between neurons in the central nervous system. The specific goals of the work proposed here are to localize receptor subunit proteins to specific islet cell populations using double immunofluorescence techniques and confocal microscopy. Electrophysiological studies will also be undertaken to determine the role of receptor activation in controlling or modulating the physiological properties of islets. Release of GABA and glutamate from islet cells will be measured in real time. To accomplish this we will use HEK 293 cells expressing recombinant GABA and glutamate receptors as molecular detectors for GABA or glutamate flowing from islets. The effects of receptor activation on insulin and glucagon secretion will be tested through column perifusion studies of isolated islet cells. These studies should improve understanding of how islet cells communicate with each other and with the central nervous system. Numerous disorders are associated with hormonal secretion deficits including type II diabetes, chronic pancreatitis, pancreatic cancer and some neurodegenerative disorders such as Huntington s Disease. This research may provide new insights into the etiology of some forms of Type II diabetes and lead to new treatments for hormone imbalance problems.