Differences of pancreatic expression of 7B2 between C57BL/6J and C3H/HeJ mice and genetic polymorphisms at its locus (Sgne1).
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.
Schmidt
Gunther
G
Diseases of Aging Program, Ottawa Health Research Institute, Ottawa Hospital, University of Ottawa, Ontario, Canada.
Sirois
Francine
F
Anini
Younes
Y
Kauri
Lisa M
LM
Gyamera-Acheampong
Charles
C
Fleck
Eckart
E
Scott
Fraser W
FW
Chrétien
Michel
M
Mbikay
Majambu
M
D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D005934:Glucagon / Q000097:blood; D018149:Glucose Intolerance / Q000235:genetics; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D051859:Neuroendocrine Secretory Protein 7B2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D045706:Proprotein Convertase 2 / Q000378:metabolism; D017510:Protein Folding; D016415:Sequence Alignment
D051859:Neuroendocrine Secretory Protein 7B2; C497679:Sgne1 protein, mouse; D005934:Glucagon; D045706:Proprotein Convertase 2