PROLONGED EXPOSURE TO GROWTH HORMONE (GH) AND IMPAIRED INSULIN SIGNALING IN THE HEART: EVIDENCE FROM GH-TRANSGENIC AND LIVER IGF1-DEFICIENT (LID) MICE

BURGHI, VALERIA; DOMINICI, FERNANDO P; MIQUET, JOHANNA G.; ANA ISABEL SOTELO; MUÑOZ, MARINA C.; CICCONI, NADIA SOFÍA; PENNISI, PATRICIA

Mar del Plata

Congreso; LXIV Reunión anual de la Sociedad Argentina de Investigaciones Clínicas (SAIC); 2019

Sociedad Argentina de Investigaciones Clínicas (SAIC)

We have previously reported that 7-month-old transgenic mice overexpressing growth hormone (GH-Tg) exhibit impaired insulin signaling in the heart, which could be related to the cardiomegaly they exhibit. Liver IGF1-deficient (LID) mice, which have a marked reduction in circulating IGF1 levels with a consequent increase in serum GH concentration, also display impaired insulin signaling in the heart. However, cardiomegaly was not observed in the LID mice studied, which were 2-4 months old. This could be due to the difference in age of the animals studied or to the IGF1 circulating levels, which are increased in GH-Tg and decreased in LID mice.Therefore, the first objective was to assess if GH-Tg mice of 2-4 months old display the same alterations previously described for older animals, in order to compare the results with those obtained for LID mice. Moreover, downstream signaling mediators that had not been studied were also analyzed. The second aim of this work was to evaluate possible mechanisms implicated in the impaired insulin signaling.Mice received an insulin injection, the heart was removed after 5 min, and immunoblotting and ELISA assays of tissue extracts were performed. Insulin-induced phosphorylation of the insulin receptor and downstream signaling mediators including IRS1, Akt, GSK3b and AS160 was decreased in the heart of GH-Tg and LID mice compared to normal controls. This was associated with higher basal phosphorylation of MAPK p38 and Erk1/2 in LID mice, and only of p38 in GH-Tg mice (P