Glucagon regulates its own synthesis by autocrine signaling

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 51; pp. 20925 - 20930
• Main Authors: Leibiger, Barbara, Moede, Tilo, Muhandiramlage, Thusitha P., Kaiser, Daniel, Sanchez, Pilar Vaca, Leibiger, Ingo B., Berggren, Per-Olof
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.12.2012; National Acad Sciences
• Subjects: Animals; Autocrine Communication; Biological Sciences; Biosynthesis; Blood Glucose - metabolism; Cellular biology; Cyclic AMP-Dependent Protein Kinases - metabolism; Diabetes; Gene expression; Gene Expression Regulation; Genes; Glucagon - biosynthesis; Glucagon - chemistry; Glucagon receptors; Glucose; Hormones; Hormones - chemistry; Humans; Insulin; Insulin - metabolism; Islets of Langerhans; Medicin och hälsovetenskap; Messenger RNA; Mice; Peptide hormones; Peptides; Peptides - chemistry; Protein Binding; Protein Kinase C - metabolism; Receptors; Receptors, Glucagon - chemistry; Receptors, Glucagon - metabolism; RNA, Messenger - metabolism; Signal Transduction
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1212870110

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 α 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.