Endocrine Abstracts

GH and IGF1 play an important role in cardiac development and function. Conditions leading to abnormal GH levels are associated with cardiovascular disease. Although acromegaly is associated with hypertension, insulin resistance, diabetes type 2 and dislipemia, several studies ascribe the heart alterations displayed by these patients to the direct action of chronically elevated GH and IGF1 levels.

Given that insulin acts as a growth factor to the heart and is important to cardiac function and considering that GH excess induces hyperinsulinemia, insulin resistance and cardiac alterations, it is of interest to analyze insulin sensitivity in this tissue under conditions of chronic GH excess. Thus, in this study we used transgenic mice over-expressing GH (Tg) that develop concentric cardiac hypertrophy associated with alterations in heart functionality, hyperinsulinemia and insulin resistance.

Mice were anaesthetized, received a bolus insulin injection via cava vein and the heart was removed after 2 min. Tg animals presented cardiomegaly and mild perivascular fibrosis in the heart. The activation and abundance of insulin signaling mediators were assessed by immunoblotting. Insulin-induced tyrosine phosphorylation of the insulin receptor (IR) was conserved in Tg mice compared with their normal littermates. However, the phosphorylation of IR substrate-1 (IRS1), its association with the regulatory subunit of the phosphatidil inositol 3′ kinase and the phosphorylation of Akt was 25, 50 and 40% decreased, respectively, in Tg mice (P<0.05, n=5). Contrary to what was detected in normal animals, insulin failed to stimulate the phosphorylation of mitogen activated protein kinases Erk1/2 in Tg mice. Protein content of the signaling mediators in study was not affected by either hormone stimulation or genotype.

We conclude that GH over-expressing Tg mice exhibit decreased sensitivity to insulin at several signaling steps downstream the IR in the heart. These may be associated with the cardiac pathology observed in these animals.