Chronic infusion of angiotensin-(1-7) improves insulin resistance and hypertension induced by a high-fructose diet in rats.
The current study was undertaken to determine whether Ang-(1-7) is effective in improving metabolic parameters in fructose-fed rats (FFR), a model of metabolic syndrome. Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or the same diet plus 10% fructose in drinking water. For the last 2 wk of a 6-wk period of either diet, control and FFR were implanted with subcutaneous osmotic pumps that delivered Ang-(1-7) (100 ng.kg(-1).min(-1)). A subgroup of each group of animals (control or FFR) underwent a sham surgery. We measured systolic blood pressure (SBP) together with plasma levels of insulin, triglycerides, and glucose. A glucose tolerance test (GTT) was performed, with plasma insulin levels determined before and 15 and 120 min after glucose administration. In addition, we evaluated insulin signaling through the IR/IRS-1/PI3K/Akt pathway as well as the phosphorylation levels of IRS-1 at inhibitory site Ser(307) in skeletal muscle and adipose tissue. FFR displayed hypertriglyceridemia, hyperinsulinemia, increased SBP, and an exaggerated release of insulin during a GTT, together with decreased activation of insulin signaling through the IR/IRS-1/PI3K/Akt pathway in skeletal muscle, liver, and adipose tissue, as well as increased levels of IRS-1 phospho-Ser(307) in skeletal muscle and adipose tissue, alterations that correlated with increased activation of the kinases mTOR and JNK. Chronic Ang-(1-7) treatment resulted in normalization of all alterations. These results show that Ang-(1-7) ameliorates insulin resistance in a model of metabolic syndrome via a mechanism that could involve the modulation of insulin signaling.
Giani
Jorge F
JF
IQUIFIB, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, (1113) Buenos Aires, Argentina.
Mayer
Marcos A
MA
Muñoz
Marina C
MC
Silberman
Ezequiel A
EA
Höcht
Christian
C
Taira
Carlos A
CA
Gironacci
Mariela M
MM
Turyn
Daniel
D
Dominici
Fernando Pablo
FP
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004032:Diet; D004353:Drug Evaluation, Preclinical; D005632:Fructose / Q000009:adverse effects* / Q000494:pharmacology; D005951:Glucose Tolerance Test / Q000662:veterinary; D006973:Hypertension / Q000139:chemically induced* / Q000517:prevention & control*; D007260:Infusion Pumps; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D007328:Insulin; D010446:Peptide Fragments; D005632:Fructose; D000803:Angiotensin I; C118790:angiotensin I (1-7)