Glucose acutely stimulates proinsulin synthesis in pancreatic β-cells through a poorly understood post-transcriptional mechanism. In the present study, we demonstrate in pancreatic β-cells that glucose stimulates the recruitment of ribosome-associated proinsulin mRNA, located in the cytoplasm, to the ER (endoplasmic reticulum), the site of proinsulin synthesis, and that this plays an important role in glucose-stimulated proinsulin synthesis. Interestingly, glucose has greater stimulatory effect on the recruitment of proinsulin mRNA to the ER compared with other mRNAs encoding secretory proteins. This, as far as we are aware, is the first example whereby mRNAs encoding secretory proteins are selectively recruited to the ER and provides a novel regulatory mechanism for secretory protein synthesis. Contrary to previous reports, and importantly in understanding the mechanism by which glucose stimulates proinsulin synthesis, we demonstrate that there is no large pool of ‘free’ proinsulin mRNA in the cytoplasm and that glucose does not increase the rate of de novo initiation on the proinsulin mRNA. However, we show that glucose does stimulate the rate of ribosome recruitment on to ribosome-associated proinsulin mRNA. In conclusion, our results provide evidence that the selective recruitment of proinsulin mRNA to the ER, together with increases in the rate of initiation are important mediators of glucose-stimulated proinsulin synthesis in pancreatic β-cells.
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Research Article|
October 10 2005
The selective recruitment of mRNA to the ER and an increase in initiation are important for glucose-stimulated proinsulin synthesis in pancreatic β-cells
Isabel C. Greenman;
Isabel C. Greenman
1Department of Cell Physiology and Pharmacology, University of Leicester, Maurice Shock Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
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Edith Gomez;
Edith Gomez
1Department of Cell Physiology and Pharmacology, University of Leicester, Maurice Shock Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
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Claire E. J. Moore;
Claire E. J. Moore
1Department of Cell Physiology and Pharmacology, University of Leicester, Maurice Shock Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
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Terence P. Herbert
Terence P. Herbert
1
1Department of Cell Physiology and Pharmacology, University of Leicester, Maurice Shock Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
1To whom correspondence should be addressed (email tph4@le.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 18 2005
Revision Received:
June 09 2005
Accepted:
June 23 2005
Accepted Manuscript online:
June 23 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 391 (2): 291–300.
Article history
Received:
March 18 2005
Revision Received:
June 09 2005
Accepted:
June 23 2005
Accepted Manuscript online:
June 23 2005
Citation
Isabel C. Greenman, Edith Gomez, Claire E. J. Moore, Terence P. Herbert; The selective recruitment of mRNA to the ER and an increase in initiation are important for glucose-stimulated proinsulin synthesis in pancreatic β-cells. Biochem J 15 October 2005; 391 (2): 291–300. doi: https://doi.org/10.1042/BJ20050468
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