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.
Paul
G L
GL
Department of Food Science and Human Nutrition, and Division of Nutritional Sciences, University of Illinois, Urbana-Champaign, IL 61801, USA.
Waegner
A
A
Gaskins
H R
HR
Shay
N F
NF
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D002461:Cell Line, Transformed; D015870:Gene Expression / Q000502:physiology*; D005934:Glucagon / Q000235:genetics*; D006639:Histidine / Q000493:pharmacokinetics*; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
D000596:Amino Acids; D011498:Protein Precursors; D012333:RNA, Messenger; D006639:Histidine; D052336:Proglucagon; D005934:Glucagon