Abstract
Pancreatic beta-cells store insulin in secretory granules that undergo exocytosis upon glucose stimulation. Sustained stimulation depletes beta-cells of their granule pool, which must be quickly restored. However, the factors promoting rapid granule biogenesis are unknown. Here we show that beta-cell stimulation induces the nucleocytoplasmic translocation of polypyrimidine tract-binding protein (PTB). Activated cytosolic PTB binds and stabilizes mRNAs encoding proteins of secretory granules, thus increasing their translation, whereas knockdown of PTB expression by RNA interference (RNAi) results in the depletion of secretory granules. These findings may provide insight for the understanding and treatment of diabetes, in which insulin secretion is typically impaired.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoantigens
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Cells, Cultured
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Diabetes Mellitus / genetics
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Diabetes Mellitus / metabolism
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Diabetes Mellitus / physiopathology
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Female
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Gene Expression / drug effects
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Glucose / metabolism
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Glucose / pharmacology
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Insulin / metabolism*
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Insulin Secretion
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Islets of Langerhans / metabolism*
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Islets of Langerhans / ultrastructure
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Microscopy, Electron
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Polypyrimidine Tract-Binding Protein / genetics
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Polypyrimidine Tract-Binding Protein / metabolism*
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Protein Binding / drug effects
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Protein Binding / genetics
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Protein Transport / drug effects
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Protein Transport / genetics
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism
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RNA Interference / physiology
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Receptor-Like Protein Tyrosine Phosphatases, Class 8
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Secretory Vesicles / drug effects
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Secretory Vesicles / metabolism*
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Secretory Vesicles / ultrastructure
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Transcriptional Activation / drug effects
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Transcriptional Activation / genetics
Substances
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Autoantigens
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Insulin
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Membrane Proteins
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RNA, Messenger
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Polypyrimidine Tract-Binding Protein
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Protein Tyrosine Phosphatases
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Ptprn protein, rat
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Receptor-Like Protein Tyrosine Phosphatases, Class 8
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Glucose