title: Glucagon regulates its own synthesis by autocrine signaling.
abstract: 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.
authors.affiliation: Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-17176 Stockholm, Sweden. ingo.leibiger@ki.se
authors.forename: Barbara
authors.initials: B
authors.lastname: Leibiger
authors.forename: Tilo
authors.initials: T
authors.lastname: Moede
authors.forename: Thusitha P
authors.initials: TP
authors.lastname: Muhandiramlage
authors.forename: Daniel
authors.initials: D
authors.lastname: Kaiser
authors.forename: Pilar
authors.initials: P
authors.lastname: Vaca Sanchez
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Leibiger
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D001786:Blood Glucose / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D005934:Glucagon / Q000096:biosynthesis* / Q000737:chemistry*; D006728:Hormones / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018027:Receptors, Glucagon / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D010455:Peptides; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D005934:Glucagon; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C