title: Translational control of glucose-induced islet amyloid polypeptide production in pancreatic islets.
abstract: Dysfunctional islet amyloid polypeptide (IAPP) biosynthesis and/or processing are thought contribute to formation of islet amyloid in type 2 diabetes. However, it is unclear how normal pro-IAPP biosynthesis and processing are regulated to be able to define such dysfunction. Here, it was found that acute exposure to high glucose concentrations coordinately regulated the biosynthesis of pro-IAPP, proinsulin, and its proprotein convertase PC1/3 in normal isolated rat islets, without affecting their respective mRNA levels. Pro-7B2 biosynthesis, like that of pro-PC2, did not appreciably change, but this was likely due to a much higher expression in pancreatic α-cells masking glucose regulation of their biosynthesis in β-cells. Biosynthesis of pro-SAAS, the putative PC1/3 chaperone, was unaffected by glucose, consistent with its scarce expression in β-cells. We conclude that translational control of pro-IAPP biosynthesis, in parallel to the pro-PC1/3, pro-PC2, and pro-7B2 proprotein-processing endopeptidases/chaperones, is the predominate mechanism to produce IAPP in islet β-cells.
authors.affiliation: The Kovler Diabetes Center, Department of Medicine, Section on Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alarcon
authors.forename: C Bruce
authors.initials: CB
authors.lastname: Verchere
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Rhodes
mesh_terms: D000682:Amyloid / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D058228:Islet Amyloid Polypeptide / Q000096:biosynthesis* / Q000235:genetics; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011384:Proinsulin / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D011384:Proinsulin; D005947:Glucose