title: Transgenic mice overexpressing Renin exhibit glucose intolerance and diet-genotype interactions.
abstract: Numerous animal and clinical investigations have pointed to a potential role of the renin-angiotensin system (RAS) in the development of insulin resistance and diabetes in conditions of expanded fat mass. However, the mechanisms underlying this association remain unclear. We used a transgenic mouse model overexpressing renin in the liver (RenTgMK) to examine the effects of chronic activation of RAS on adiposity and insulin sensitivity. Hepatic overexpression of renin resulted in constitutively elevated plasma angiotensin II (four- to six-fold increase vs. wild-type, WT). Surprisingly, RenTgMK mice developed glucose intolerance despite low levels of adiposity and insulinemia. The transgenics also had lower plasma triglyceride levels. Glucose intolerance in transgenic mice fed a low-fat diet was comparable to that observed in high-fat fed WT mice. These studies demonstrate that overexpression of renin and associated hyperangiotensinemia impair glucose tolerance in a diet-dependent manner and further support a consistent role of RAS in the pathogenesis of diabetes and insulin resistance, independent of changes in fat mass.
authors: Genome Science and Technology Program, University of Tennessee Knoxville, TN, USA.
authors: Sarah J
authors: SJ
authors: Fletcher
authors: Nishan S
authors: NS
authors: Kalupahana
authors: Morvarid
authors: M
authors: Soltani-Bejnood
authors: Jung Han
authors: JH
authors: Kim
authors: Arnold M
authors: AM
authors: Saxton
authors: David H
authors: DH
authors: Wasserman
authors: Bart
authors: B
authors: De Taeye
authors: Brynn H
authors: BH
authors: Voy
authors: Annie
authors: A
authors: Quignard-Boulange
authors: Naima
authors: N
authors: Moustaid-Moussa
keywords: adipose tissue; angiotensin II; insulin resistance; renin-angiotensin system