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


     

DOI: 10.1530/eje.0.1360107
European Journal of Endocrinology, Vol 136, Issue 1, 107-113
Copyright © 1997 by European Society of Endocrinology
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by van Hulst, K. L
Right arrow Articles by Höppener, J. W.
Right arrow Search for Related Content
PubMed
Right arrow Articles by van Hulst, K. L
Right arrow Articles by Höppener, J. W.

Biologically active human islet amyloid polypeptide/amylin in transgenic mice

Karen L van Hulst, Walter Born, Roman Muff, Cor Oosterwijk, Marinus A Blankenstein, Cornelis JM Lips, Jan A Fischer and Jo WM Höppener

Objective: Human islet amyloid polypeptide (hIAPP), also named amylin, is a pancreatic β cell protein implicated in the pathogenesis of pancreatic islet amyloid formation and type 2 diabetes mellitus. To study the (patho)physiological roles of hIAPP, we have generated transgenic mice that overexpress hIAPP mRNA, in relation to endogenous mouse IAPP (mIAPP) mRNA, in pancreatic β cells. The biological activity of human and mouse IAPP derived from pancreatic extracts was determined.

Methods: Pancreatic and plasma extracts of transgenic and control mice were analyzed by reversedphase high-performance liquid chromatography (HPLC) and radioimmunoassay, yielding a separation of hIAPP from mIAPP. Biological activity of immunoreactive human and mouse IAPP components derived from pancreatic extracts was assessed by calcitonin receptor-mediated stimulation of cyclic AMP accumulation in T47D human breast carcinoma cells.

Results: The predominant immunoreactive human and mouse IAPP gene products had the retention times on HPLC analysis of the corresponding synthetic peptides. The ratio of bioactive over immunoreactive hIAPP and mIAPP was 0·93 ±0·18 and 1·19 ±0·56 respectively. In extracts of two plasma pools from 4 transgenic animals, hIAPP was 4·6- to 7-fold more abundant than mIAPP.

Conclusion; This study has shown that correctly processed hIAPP produced in transgenic mouse pancreatic β cells exhibits full biological activity. The results validate these transgenic mice for the study of (patho)physiological roles of hIAPP in vivo.

European Journal of Endocrinology 136 107–113






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1997 European Society of Endocrinology.