Histidine availability alters glucagon gene expression in murine alphaTC6 cells

Because individual amino acids (AA) stimulate glucagon release from pancreatic alpha-cells, the purpose of this study was to determine if individual AA could influence glucagon gene expression. Preproglucagon mRNA levels were 67% lower (P < 0.05) in mouse alphaTC6 cells incubated for 12 h in amino acid-free medium compared with cells incubated in complete medium containing all 20 AA. A time-course study indicated that alphaTC6 cells incubated in amino acid-free medium +/-1 micromol/L puromycin or amino acid-containing medium plus puromycin exhibited similar preproglucagon mRNA decreases over 12 h. When 1 micromol/L actinomycin was added to medium with or without AA, ppG mRNA concentrations decreased (P < 0.05) for 3h; however, values at 12 h were not different than those at 3 h. Deletions of single AA from complete medium demonstrated that only histidine removal or depletion reproduced the decrease in ppG mRNA observed in amino acid-free medium. We conclude that histidine is involved in the regulation of preproglucagon mRNA levels in alphaTC6 cells and that this regulation may be operative during both transcriptional and post-transcriptional events.