JBC Oz Biosciences

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Verchere, C. B.
Right arrow Articles by Halban, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Verchere, C. B.
Right arrow Articles by Halban, P. A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Volume 271, Number 44, Issue of November 1, 1996 pp. 27475-27481
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

Des-(, , , , )C-Peptide
A NOVEL SECRETORY PRODUCT OF THE RAT PANCREATIC BETA CELL PRODUCED BY TRUNCATION OF PROINSULIN CONNECTING PEPTIDE IN SECRETORY GRANULES

(Received for publication, January 11, 1996, and in revised form, May 21, 1996)

C. Bruce Verchere Dagger , Michel Paoletta , Marguerite Neerman-Arbez , Keith Rose par , Jean-Claude Irminger , Ronald L. Gingerich '' , Steven E. Kahn Dagger and Philippe A. Halban

From the Dagger  Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, Veterans Affairs Medical Center and University of Washington, Seattle, Washington 98108, the  Louis Jeantet Research Laboratories and par  Department of Medical Biochemistry, University of Geneva Medical Center, 1211 Geneva 4, Switzerland, and '' Linco Research Inc., Saint Charles, Missouri 63304

Insulin and connecting peptide (C-peptide) are produced in equimolar amounts during proinsulin conversion in the pancreatic beta cell secretory granule. To determine whether insulin and C-peptide are equally stable in beta cell granules (and thus secreted in equimolar amounts), neonatal and adult rat beta cells were pulse-chased, and radiolabeled insulin and C-peptide analyzed by high performance liquid chromatography. A novel truncated C-peptide was identified and shown by mass spectrometry to be des-(, , , , )C-peptide (loss of 5 C-terminal amino acids). Des-(, , , , )C-peptide is a major beta cell secretory product, accounting for 37.4 ± 1.6% (neonatal) and 8.5 ± 0.6% (adult) of total labeled C-peptide in secretory granules after 10 h of chase. Des-(, , , , )C-peptide is also secreted in a glucose-sensitive manner from the perfused adult rat pancreas, accounting for ~10% of total C-peptide immunoreactivity secreted. Human C-peptide is also a substrate for truncation in granules. Thus, when human proinsulin was expressed (infection with recombinant adenovirus) in transformed (INS) rat beta cells, human des-(, , , , )C-peptide was secreted along with the intact human peptide and both intact and truncated rat C-peptide. In addition to truncation, 33.1 ± 1.2% of C-peptide in neonatal but not adult rat beta cell granules was further degraded. Such degradation was completely inhibited by ammonium chloride (known to neutralize intra-granular pH), whereas truncation was only partially inhibited by ~50%. In conclusion, a novel beta cell secretory product, des-(, , , , )C-peptide, has been identified and should be considered as a potential bioactive peptide. Both truncation and degradation of C-peptide are responsible for non-equimolar secretion of insulin and C-peptide in rat beta cells.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 EndocrinologyHome page
F. Jaques, H. Jousset, A. Tomas, A.-L. Prost, C. B. Wollheim, J.-C. Irminger, N. Demaurex, and P. A. Halban
Dual Effect of Cell-Cell Contact Disruption on Cytosolic Calcium and Insulin Secretion
Endocrinology, May 1, 2008; 149(5): 2494 - 2505.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
E. Rogatsky, B. Balent, G. Goswami, V. Tomuta, H. Jayatillake, G. Cruikshank, L. Vele, and D. T. Stein
Sensitive Quantitative Analysis of C-Peptide in Human Plasma by 2-Dimensional Liquid Chromatography-Mass Spectrometry Isotope-Dilution Assay
Clin. Chem., May 1, 2006; 52(5): 872 - 879.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. Molinete, S. Dupuis, F. M. Brodsky, and P. A. Halban
Role of clathrin in the regulated secretory pathway of pancreatic {beta}-cells
J. Cell Sci., March 10, 2002; 114(16): 3059 - 3066.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.