期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 51, 页码 20925-20930出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1212870110
关键词
gene expression; signal transduction
资金
- Swedish Research Council
- Novo Nordisk Foundation
- Karolinska Institutet
- Swedish Diabetes Association
- Knut and Alice Wallenberg Foundation
- European Foundation for the Study of Diabetes
- Diabetes Research and Wellness Foundation
- Bert von Kantzow Foundation
- Skandia Insurance Company, Ltd.
- World Class University program through the National Research Foundation of Korea
- Ministry of Education, Science and Technology [CR31-2008-000-10105-0]
- Stichting af Jochnick Foundation
- Erling-Persson Family Foundation
- Juvenile Diabetes Research Foundation [31-2008-413]
- [FP7-228933-2]
- Novo Nordisk Fonden [NNF12OC1016557] Funding Source: researchfish
Peptide hormones are powerful regulators of various biological processes. To guarantee continuous availability and function, peptide hormone secretion must be tightly coupled to its biosynthesis. A simple but efficient way to provide such regulation is through an autocrine feedback mechanism in which the secreted hormone is sensed by its respective receptor and initiates synthesis at the level of transcription and/or translation. Such a secretion-biosynthesis coupling has been demonstrated for insulin; however, because of insulin's unique role as the sole blood glucose-decreasing peptide hormone, this coupling is considered an exception rather than a more generally used mechanism. Here we provide evidence of a secretion-biosynthesis coupling for glucagon, one of several peptide hormones that increase blood glucose levels. We show that glucagon, secreted by the pancreatic a cell, up-regulates the expression of its own gene by signaling through the glucagon receptor, PKC, and PKA, supporting the more general applicability of an autocrine feedback mechanism in regulation of peptide hormone synthesis.
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