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An important feature of glucose homeostasis is the effective release of glucagon from the pancreatic alpha cell. The molecular mechanisms regulating glucagon secretion are still poorly understood. We now demonstrate that human alpha cells express ionotropic glutamate receptors (iGluRs) that are essential for glucagon release. A lowering in glucose concentration results in the release of glutamate from the alpha cell. Glutamate then acts on iGluRs of the AMPA/kainate type, resulting in membrane depolarization, opening of voltage-gated Ca(2+) channels, increase in cytoplasmic free Ca(2+) concentration, and enhanced glucagon release. In vivo blockade of iGluRs reduces glucagon secretion and exacerbates insulin-induced hypoglycemia in mice. Hence, the glutamate autocrine feedback loop endows the alpha cell with the ability to effectively potentiate its own secretory activity. This is a prerequisite to guarantee adequate glucagon release despite relatively modest changes in blood glucose concentration under physiological conditions.

BALB/c mice were intramuscularly immunized with low doses (25-50microg) of DNA cocktail containing plasmids encoding the full-length SAG1/P30 and the 196-561 terminal sequence of ROP2 genes. This immunization resulted in a Th1-type response with predominance of IgG2a and a specific T-cell proliferation with high levels of interferon-gamma (IFN-gamma) secretion, whereas no IL-4 was detected. Moreover, DNA cocktail immunization induced a long-lasting protection against a lethal challenge with the highly virulent Toxoplasma gondii RH strain, whereas low doses of single genes were not protective. These results support further investigations to achieve a multigene anti-T. gondii DNA vaccine.

An expression genomic library of Trypanosoma cruzi (T. cruzi) constructed using pcDNA3 plasmid was used for the immunisation (25 ug) of Balblc mice. Expression of T. cruzi antigens in the muscle of inoculated mice was detected by indirect immunofluorescence 7 days after immunisation. Specific IgG antibodies were significatively increased (P ~0.05) in animals that were reimmunised with 50 ,ug of the genomic library. An antigen specific lymphoproliferative response was detected in one animal of 0 1998 Elsevier Science Ltd. All the group inoculated with one dose of the library rights reserved