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The balance between proinsulin biosynthesis and insulin secretion: where can imbalance lead?
- Source :
-
Diabetes, Obesity & Metabolism . Nov2007 Supplement 2, Vol. 9, p56-66. 11p. 2 Diagrams, 2 Charts, 2 Graphs. - Publication Year :
- 2007
-
Abstract
- Insulin is stored in pancreatic β-cells in β-granules. Whenever insulin is secreted in response to a nutrient secretagogue, there is a complementary increase in proinsulin biosynthesis to replenish intracellular insulin stores. This specific nutrient regulation of proinsulin biosynthesis is predominately regulated at the translational level. Recently, a highly conserved cis-element in the 5′-untranslated region (UTR) of preproinsulin mRNA, named ppIGE, has been identified that is required for specific translational regulation of proinsulin biosynthesis. This ppIGE is also found in the 5′-UTR of certain other translationally regulated β-granule protein mRNAs, including the proinsulin processing endopeptidases, PC1/3 and PC2. This provides a mechanism whereby proinsulin processing is adaptable to changes in proinsulin biosynthesis. However, relatively few β-granules undergo secretion, with most remaining in the storage pool for ∼5 days. Aged β-granules are retired by intracellular degradation mechanisms, either via crinophagy and/or autophagy, as another long-term means of maintaining β-granule stores at optimal levels. When a disconnection between insulin production and secretion arises, as may occur in type 2 diabetes, autophagy further increases to maintain β-granule numbers. However, if this increased autophagy becomes chronic, autophagia-mediated cell death occurs that could then contribute to β-cell loss in type 2 diabetes. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14628902
- Volume :
- 9
- Database :
- Academic Search Index
- Journal :
- Diabetes, Obesity & Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 26913427
- Full Text :
- https://doi.org/10.1111/j.1463-1326.2007.00774.x