Characterization of vesicular glutamate transporter in pancreatic - and -cells and its regulation by glucose

Bai, Liqun, Xiaohong Zhang, and Fayez K. Ghishan. Characterization of vesicular glutamate transporter in pancreatic and -cells and its regulation by glucose. Am J Physiol Gastrointest Liver Physiol 284: G808–G814, 2003. First published November 20, 2002; 10.1152/ajpgi.00333. 2002.—Glutamate has been suggested to play an important role in the 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 -2) have recently been cloned from the brain. In this report, we first functionally characterized vesicular glutamate transporter in cultured pancreatic and -cells, and then detected mRNA expression of VGLUT1 and -2 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 and -cells contain functional vesicular glutamate transporter. The transport characteristics are similar to the cloned neuronal VGLUT1 and -2 in regard to ATP dependence, substrate specificity, kinetics, and chloride dependence. VGLUT2 mRNA is expressed in both and -cells, whereas VGLUT1 is only expressed in -cells. High (12.8 mM) and low (2.8 mM) concentrations of glucose increased vesicular glutamate transport in and -cells, respectively. VGLUT2 mRNA was significantly increased in and -cells by high and low glucose concentration, respectively. This increase in VGLUT2 mRNA was suppressed by actinomycin D. We conclude that both and -cells possess functional vesicular glutamate transporters regulated by alteration in glucose concentration, partly via the transcriptional mechanism.