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GABA, an extracellular marker for nutrient metabolism in pancreatic beta cells

Wednesday, 14 June, 2006 - 17:00
Campus: Brussels Health Campus
Faculty: Medicine and Pharmacy
auditorium P. Brouwer
Chen Wang
phd defence

Preparation of a therapeutic beta cell graft requires
the availability of adequate quality control.
Processes of cell death can be associated with
depletion and/or discharge of cell specific
substances which can then be picked up and
measured through assaying these compounds.
Gamma aminobutyric acid (GABA) is synthesized
and released by pancreatic beta cells with a higher
turnover rate and a smaller intracellular fraction.
We have investigated potential use of GABA as a
marker for the functional beta cell mass. This work
has resulted in the following three sets of
conclusions: 1) Beta cells were the major source of
GABA formation in pancreatic tissue. Cellular and
medium GABA rapidly and markedly declined
within 24h following beta cell exposure to
cytotoxic agents whereas the insulin content
remained unchanged. 2) Nutrients influence GABA
release through changes in substrate availability.
Glutamine causes a dose-dependent increase in
GABA release while glucose metabolism decreased
GABA release through activation of GABA-T. 3)
GABA release was increased by cAMP generators
through activation of protein kinase A. This effect
could not be blocked by GABA-T inhibitor, but
inhibited by GAD inhibitor. These observations
indicate that extracellular GABA levels are a
sensitive marker for the presence of living beta
cells and for their metabolic activities, in particular
their nutrient-driven functional state. Acute and
chronic changes in GABA release can be used to
assess the effects of glucose and cyclic AMP on
nutrient metabolism in beta cells.