Insulin Gene Expression and Biosynthesis

作者: Vincent Poitout , Roland Stein , Christopher J. Rhodes

DOI: 10.1002/9781118387658.CH6

关键词: ProinsulinInsulinInsulin receptor substrateEndocrinologyProprotein convertase 2PreproinsulinGRB10Internal medicineProhormone convertaseBiologyInsulin receptor

摘要: The insulin gene is expressed specifically and at very high levels in pancreatic β-cells. Most of its tissue-specific expression metabolic regulation are conferred by approximately 340 bp upstream the transcription initiation site. Several glucose-responsive elements have been identified within this region, physiological relies on cooperative synergistic interactions between DNA-binding factors coactivators. Glucose major regulator expression. It activates stabilizes mRNA. In addition, stimulated glucagon-like peptide 1, growth hormone, lactogenic hormones, inhibited epinephrine, somatostatin, glucagon, leptin. type 2 diabetes, chronic elevations blood glucose fatty acid impair Under most circumstances, production also highly regulated translational level. Indeed, predominant control mechanism β-cell whereby intracellular stores efficiently maintained short term. Essentially, translation preproinsulin mRNA template to protein occurs a fashion typical eukaryotic mRNAs. general, nutrients that stimulate secretion, which physiologically relevant, proinsulin biosynthesis Recently, it has shown specific glucose-induced resides cis-elements 5′- 3′-untranslated regions itself. After translocated into lumen rough endoplasmic reticulum, correctly folded can then be delivered transport vesicles cis-Golgi apparatus an ATP-dependent process. site for processing biologically active immature granule compartment β-cell. Production via limited proteolysis precursor molecule, catalyzed two endopeptidases, proprotein convertase (PC2) 3 (PC3) (also known as PC-1), exopeptidase, carboxypeptidase-H (CP-H). Similar their deleterious effects expression, hyperglycemia hyperlipidiemia biosynthesis. Keywords: insulin gene; promoter; transcription factor; proinsulin; translation; biosynthesis; hyperglycemia; hyperlipidemia

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