title: Angiotensin 1-7 improves insulin sensitivity by increasing skeletal muscle glucose uptake in vivo.
abstract: The renin-angiotensin system (RAS) regulates skeletal muscle insulin sensitivity through different mechanisms. The overactivation of the ACE (angiotensin-converting enzyme)/Ang (angiotensin) II/AT1R (Ang II type 1 receptor) axis has been associated with the development of insulin resistance, whereas the stimulation of the ACE2/Ang 1-7/MasR (Mas receptor) axis improves insulin sensitivity. The in vivo mechanisms by which this axis enhances skeletal muscle insulin sensitivity are scarcely known. In this work, we investigated whether rat soleus muscle expresses the ACE2/Ang 1-7/MasR axis and determined the effect of Ang 1-7 on rat skeletal muscle glucose uptake in vivo. Western blot analysis revealed the expression of ACE2 and MasR, while Ang 1-7 levels were detected in rat soleus muscle by capillary zone electrophoresis. The euglycemic clamp exhibited that Ang 1-7 by itself did not promote glucose transport, but it increased insulin-stimulated glucose disposal in the rat. In a similar manner, captopril (an ACE inhibitor) enhanced insulin-induced glucose uptake and this effect was blocked by the MasR antagonist A-779. Our results show for the first time that rat soleus muscle expresses the ACE2/Ang 1-7/MasR axis of the RAS, and Ang 1-7 improves insulin sensitivity by enhancing insulin-stimulated glucose uptake in rat skeletal muscle in vivo. Thus, endogenous (systemic and/or local) Ang 1-7 could regulate insulin-mediated glucose transport in vivo.
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Sede Sur, Mexico City, Mexico.
authors.forename: Omar
authors.initials: O
authors.lastname: Echeverría-Rodríguez
authors.affiliation: Departamento de Farmacología, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Del Valle-Mondragón
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Sede Sur, Mexico City, Mexico. Electronic address: enriquehong@hotmail.com.
authors.forename: Enrique
authors.initials: E
authors.lastname: Hong
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7); D005947:Glucose
keywords: Angiotensin 1–7; Angiotensin-converting enzyme 2 (ACE2); Glucose uptake; Mas receptor; Renin–angiotensin system (RAS); Skeletal muscle