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Histidine availability alters glucagon gene expression in murine alphaTC6 cells
G L Paul1, A Waegner, H R Gaskins
1Department of Food Science and Human Nutrition, and Division of Nutritional Sciences, University of Illinois, Urbana-Champaign, IL 61801, USA.
The Journal of Nutrition
|June 18, 1998
Summary
This study found that histidine is crucial for regulating glucagon gene expression in pancreatic alpha cells. Removing histidine significantly reduced preproglucagon mRNA levels, indicating its role in controlling glucagon production.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Individual amino acids (AA) are known to stimulate glucagon release from pancreatic alpha-cells.
- The precise mechanisms by which amino acids influence glucagon gene expression remain incompletely understood.
Purpose of the Study:
- To investigate whether individual amino acids can modulate glucagon gene expression.
- To identify specific amino acids involved in the regulation of preproglucagon mRNA levels.
Main Methods:
- Mouse alphaTC6 alpha-cells were cultured in media with varying amino acid compositions.
- Preproglucagon mRNA levels were quantified using quantitative PCR.
- Experiments involved amino acid deprivation, puromycin (protein synthesis inhibitor), and actinomycin (transcription inhibitor) treatments.
Main Results:
- Incubation in amino acid-free medium for 12 hours resulted in a 67% decrease in preproglucagon mRNA levels compared to complete medium.
- Puromycin treatment showed similar preproglucagon mRNA decreases in both amino acid-free and complete media.
- Actinomycin treatment caused an initial decrease in mRNA, with levels stabilizing after 3 hours.
- Selective removal of histidine from the complete medium mimicked the reduction in preproglucagon mRNA observed in amino acid-free conditions.
Conclusions:
- Histidine plays a significant role in regulating preproglucagon mRNA levels in pancreatic alphaTC6 cells.
- This regulation by histidine appears to involve both transcriptional and post-transcriptional mechanisms.
- These findings highlight a specific amino acid's importance in controlling glucagon gene expression.