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Diabetes 55:452-459, 2006
DOI: 10.2337/diabetes.55.02.06.db05-0733
© 2006 by the American Diabetes Association
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Islet Study

Differences of Pancreatic Expression of 7B2 Between C57BL/6J and C3H/HeJ Mice and Genetic Polymorphisms at its locus (Sgne1)

Gunther Schmidt1,2, Francine Sirois1, Younes Anini1, Lisa M. Kauri3, Charles Gyamera-Acheampong1, Eckart Fleck2, Fraser W. Scott2, Michel Chrétien1, and Majambu Mbikay1

1 Diseases of Aging Program, Ottawa Health Research Institute, Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
2 Department of Medicine, Deutsches Herzzentrum, Berlin, Germany
3 Molecular Medicine Program, Ottawa Health Research Institute, Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada

Address correspondence and reprint requests to Majambu Mbikay, PhD, Diseases of Aging Program, Ottawa Health Research Institute, Ottawa Hospital, University of Ottawa, 725 Parkdale Ave., Ottawa, Ontario, Canada K1Y 4E9. E-mail: mmbikay{at}ohri.ca

Key Words: EGFP, enhanced green fluorescent protein • GADPH, glyceraldehyde-3-phosphate dehydrogenase • MF, mean fluorescence • PC, proprotein convertase

C57BL/6 (B6) mice develop glucose intolerance with age, whereas C3H/He (C3H) mice do not. In this study, we examined whether this differential glucose homeostasis was associated with differences of proteolytic activation of pancreatic prohormones. Radioimmunoassays showed comparable levels of fasting plasma insulin between the two strains but a significantly lower glucagon level in B6 mice. Pulse-chase analysis of glucagon biosynthesis in isolated pancreatic islets revealed that proglucagon was less efficiently processed in B6 mice. Because proprotein convertase (PC)2 and its 7B2 helper protein are required for this processing, we quantified islet mRNA levels by RT-PCR and protein levels by immunoblotting. The levels of proPC2 mRNA were similar between the two strains, but B6 protein extracts contained less of the mature PC2. In contrast, 7B2 mRNA and protein levels were both significantly lower in B6 pancreas. Sequencing of the 7B2 gene promoter and cDNA in the two strains revealed seven single nucleotide polymorphisms and one dinucleotide insertion/deletion in the cDNA as well as a single nucleotide polymorphism and two insertions/deletions in the promoter. Differential expression of 7B2 may contribute to the difference between B6 and C3H mice not only in glucagon production and secretion but also in glucose tolerance.


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Copyright © 2006 by the American Diabetes Association.