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Overexpression of renin in the liver impairs glucose tolerance
Author(s) -
SoltaniBejnood Morvarid,
Fletcher Sarah,
Morris Jeffrey,
Das Suchita,
Voy Brynn H.,
MoustaidMoussa Naima
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a831
Subject(s) - endocrinology , medicine , adipose tissue , diabetes mellitus , adipokine , renin–angiotensin system , genetically modified mouse , biology , transgene , type 2 diabetes , impaired glucose tolerance , angiotensin ii , receptor , gene , insulin resistance , blood pressure , biochemistry
Animal and clinical studies have pointed to a potential role of the Renin Angiotensin System (RAS) in diabetes. However, mechanisms underlying this association are not completely understood. The objective of this work is to dissect the mechanisms by which overexpression of RAS mediates glucose intolerance, using a transgenic mouse model overexpressing renin in the liver (RenTg; Caron et al., 2002), resulting in constitutively elevated plasma angiotensin II (Ang II). Twenty week‐old RenTg mice exhibit significantly impaired glucose tolerance and fasting insulinemia, despite normal glycemia, leptinemia and adiponectinemia, as compared to their wild type littermates. Although adipokine gene expression did not differ across genotypes, the type 2 Ang II receptor was markedly down‐regulated in adipose tissue of RenTg mice. Comparative proteomics of adipose tissue from these mice indicates a genotype‐dependent differential expression of several proteins associated with diabetes and glucose metabolism. We are currently studying these candidate proteins to identify their role in RAS‐induced diabetes. These studies demonstrate that overexpression of renin impairs glucose tolerance and further support the role of RAS in the pathogenesis of diabetes. Future studies will dissect mechanism(s) and tissue(s) linking RAS to diabetes. This work was supported by the TN agricultural experiment station and by the Office of Science, U.S. Dept. of Energy.