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Am J Physiol Gastrointest Liver Physiol (November 20, 2002). doi:10.1152/ajpgi.00333.2002
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Articles in PresS, published online ahead of print November 20, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00333.2002
Submitted on August 8, 2002
Accepted on November 18, 2002

Characterization of Vesicular Glutamate Transporter in Pancretic alpha and beta cells and Its Regulation by Glucose

Liqun Bai1, Xiaohong Zhang2, and Fayez K. Ghishan1*

1 Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, AZ, USA; Department of Physiology, University of Arizona Health Sciences, Tucson, AZ, USA
2 Department of Physiology, University of Arizona Health Sciences, Tucson, AZ, USA

* To whom correspondence should be addressed. E-mail: fghishan{at}peds.arizona.edu.

Glutamate has been suggested to play an important role in release of insulin and glucagon from pancreatic cells via exocytosis. Vesicular glutamate transporter is a rate-limiting step for glutamate release and is involved in the glutamate-evoked exocytosis. Two vesicular glutamate transporters (VGLUT1 and VGLUT2) have recently been cloned from brain. In this report, we first functionally characterized vesicular glutamate transporter in cultured pancreatic {alpha} and {beta} cells, and then detected mRNA expression of VGLUT1 and VGLUT2 in these cells. We also investigated the effect of high or low level of glucose on vesicular glutamate transport in cultured pancreas cells. Our results suggest that both {alpha} and {beta} cells contain functional vesicular glutamate transporter. The transport characteristics are similar to the cloned neuronal VGLUT1 and VGLUT2 in regard to ATP-dependence, substrate specificity, kinetics, and chloride dependence. VGLUT2 mRNA is expressed in both {alpha} and {beta} cells, while VGLUT1 is only expressed in {beta} cells. High (12.8 mM) and low (2.8 mM) concentrations of glucose increased vesicular glutamate transport in {beta} and {alpha} cells, respectively. VGLUT2 mRNA was significantly increased in {beta} and {alpha} cells, by high and low glucose concentration, respectively. This increase in VGLUT2 mRNA was suppressed by actinomycin D. We conclude that both {alpha} and {beta} cells possess functional vesicular glutamate transporters which are regulated by alteration in glucose concentration, partly via transcriptional mechanisms.




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