PERSONAL DE APOYO
MUÑOZ marina Cecilia
congresos y reuniones científicas
Título:
Angiotensin-(1-7) improves insulin signal transduction and inhibits growth promoting signaling pathways in heart of fructose fed rats
Autor/es:
GIANI JF; MUÑOZ MC; MAYER MA; BURGHI V; TURYN D; DOMINICI FP
Lugar:
Washington DC, EE.UU.
Reunión:
Congreso; Endocrine Society 91st Annual meeting; 2009
Institución organizadora:
Endocrine Society
Resumen:
<!--
/* Font Definitions */
@font-face
{font-family:"Cambria Math";
panose-1:2 4 5 3 5 4 6 3 2 4;
mso-font-charset:0;
mso-generic-font-family:roman;
mso-font-pitch:variable;
mso-font-signature:-1610611985 1107304683 0 0 159 0;}
@font-face
{font-family:Calibri;
panose-1:2 15 5 2 2 2 4 3 2 4;
mso-font-charset:0;
mso-generic-font-family:swiss;
mso-font-pitch:variable;
mso-font-signature:-1610611985 1073750139 0 0 159 0;}
/* Style Definitions */
p.MsoNormal, li.MsoNormal, div.MsoNormal
{mso-style-unhide:no;
mso-style-qformat:yes;
mso-style-parent:"";
margin:0cm;
margin-bottom:.0001pt;
line-height:150%;
mso-pagination:widow-orphan;
font-size:11.0pt;
font-family:"Calibri","sans-serif";
mso-ascii-font-family:Calibri;
mso-ascii-theme-font:minor-latin;
mso-fareast-font-family:Calibri;
mso-fareast-theme-font:minor-latin;
mso-hansi-font-family:Calibri;
mso-hansi-theme-font:minor-latin;
mso-bidi-font-family:"Times New Roman";
mso-bidi-theme-font:minor-bidi;
mso-fareast-language:EN-US;}
.MsoChpDefault
{mso-style-type:export-only;
mso-default-props:yes;
mso-ascii-font-family:Calibri;
mso-ascii-theme-font:minor-latin;
mso-fareast-font-family:Calibri;
mso-fareast-theme-font:minor-latin;
mso-hansi-font-family:Calibri;
mso-hansi-theme-font:minor-latin;
mso-bidi-font-family:"Times New Roman";
mso-bidi-theme-font:minor-bidi;
mso-fareast-language:EN-US;}
.MsoPapDefault
{mso-style-type:export-only;
line-height:150%;}
@page Section1
{size:612.0pt 792.0pt;
margin:70.85pt 3.0cm 70.85pt 3.0cm;
mso-header-margin:36.0pt;
mso-footer-margin:36.0pt;
mso-paper-source:0;}
div.Section1
{page:Section1;}
-->
Background Alterations
within the renin-angiotensin system (RAS) are an important contributor to the
development of insulin resistance (1) and cardiac hypertrophy (2). The RAS is
composed of two arms. The first arm is represented by angiotensin (Ang) II
which contributes to the development of insulin resistance in several tissues
and leads to cardiac remodeling by inducing the activation of several
molecules, including ERK1/2 and RhoA kinase. The second arm is antihypertensive
and antihypertrophic, where the major participant is Ang-(1-7), an heptapeptide
that constitutes an important functional end-product of the RAS (3).
Accordingly, in the present study we examined whether chronic treatment with
Ang-(1-7) restores insulin signaling and inhibits growth-promoting pathways in
fructose-fed rats, an animal model of insulin resistance with elevated
circulating levels of Ang II (4). Methods. Six-week-old male Sprague-Dawley
rats were fed either normal rat chow (control) or the same diet plus 10%
fructose in drinking water (FFR). For the last 2 weeks of a 6-week period of
either diet, control and FFR where implanted with subcutaneous osmotic pumps
that delivered Ang-(1-7) (100ng.kg-1.min-1). A subgroup of each group of
animals (control or FFR) underwent a sham surgery. By immunoblotting, we
evaluate insulin signaling through the insulin receptor (IR)/IR substrate
(IRS)-1/phosphatidylinositol-3 kinase (PI3K)/Akt pathway after an acute
administration of insulin via vena cava. To further evaluate the activation of
growth-promoting enzymes, basal phosphorylation levels of ERK1/2 and RhoA were
also determined by immunoblotting. Results. FFR displayed higher circulating
levels of Ang II, as measured by RIA, that remained unaltered after Ang-(1-7)
treatment.
An impairment in all steps of insulin signaling analyzed IR, IRS-1, p85-IRS-1
association and Akt phosphorylation (53 ,63 ,68 and 55% of control values
respectively) was detected in heart after acute insulin stimulation.
Interestingly, significant improvement in this pathway was detected after
Ang-(1-7) treatment. FFR showed a significant increase in phospho-ERK1/2 and
phospho-RhoA levels (1.9 and 2.5 fold increase over control values
respectively) which decreased significantly after Ang-(1-7) treatment. Conclusion
Chronic Ang-(1-7) treatment resulted in a restoration of insulin signaling
through the IR/IRS-1/PI3K/Akt pathway and attenuated the growth-promoting
pathways in the heart, without affecting Ang II plasma levels. References: (1)
Henriksen EJ et al., Am J Physiol Regulatory Integrative Comp Physiol 2007;
293:R974 (2) Mehta PK et al., Am J Physiol Cell Physiol 2007; 292:C82 (3)
Ferrario CM et al., Am J Physiol Heart Circ Physiol 2005; 289:H2281 (4)
Kobayashi R et al., Hypertension 1993; 21:1051