Chronic infusion of angiotensin-(1-7) improves insulin

J. F. GIANI; M. A. MAYER; M. C. MUÑOZ; E. A. SILBERMAN; C. HÖCHT; C. TAIRA; M. GIRONACCI; D. TURYN; F. P. DOMINICI

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

Año: 2009 vol. 296 p. 262 - 271

0193-1849

The current study was undertaken to determine whether Ang-(1-7) iseffective in improving metabolic parameters in fructose-fed rats (FFR), a model ofmetabolic syndrome. Six-week-old male Sprague-Dawley rats were fed either normalrat chow (control) or the same diet plus 10% fructose in drinking water. For the last 2weeks of a 6-week period of either diet, control and FFR were implanted withsubcutaneous osmotic pumps that delivered Ang-(1-7) (100 ng ⋅ kg-1 ⋅ min-1). Asubgroup of each group of animals (control or FFR) underwent a sham surgery. Wemeasured systolic blood pressure (SBP), together with plasma levels of insulin,triglycerides, and glucose. A glucose tolerance test (GTT) was performed, with plasmainsulin levels determined before, 15 and 120 min after glucose administration. Inaddition, we evaluated insulin signaling through the IR/IRS-1/PI3K/Akt pathway aswell as the phosphorylation levels of IRS-1 at inhibitory site Ser307 in skeletal muscle,and adipose tissue. FFR displayed hypertriglyceridemia, hyperinsulinemia, increasedSBP, an exaggerated release of insulin during a GTT, together with decreased activationof insulin signaling through the IR/IRS-1/PI3K/Akt pathway in skeletal muscle, liverand adipose tissue as well as increased levels of IRS-1 phosphoSer307 in skeletalmuscle and adipose tissue, alterations that correlated with increased activation of thekinases mTOR and JNK. Chronic Ang-(1-7) treatment resulted in normalization of allalterations. These results show that Ang-(1-7) ameliorates insulin resistance in a modelof metabolic syndrome via a mechanism that could involve the modulation of insulinsignaling.