Prolonged exposure to growth hormone (GH) and impaired insulin signaling in the heart: evidence from GH-transgenic and liver igf1-deficient (LID) mice

VALERIA BURGHI; NADIA CICCONI; ANA I SOTELO; FERNANDO P DOMINICI; PATRICIA A. PENNISI; MARINA C MUÑOZ; JOHANNA G MIQUET

Mar del Plata

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

SAIC

Abstract/Resumen: We have previously reported that 7-month-old transgenic mice overexpressing growth hormone (GHTg) exhibit impaired insulin signaling in the heart, which could berelated to the cardiomegaly they exhibit. Liver IGF1-deficient(LID) mice, which have a marked reduction in circulating IGF1levels 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, whichwere 2-4 months old. This could be due to the difference in ageof the animals studied or to the IGF1 circulating levels, which areincreased in GH-Tg and decreased in LID mice. Therefore, thefirst objective was to assess if GH-Tg mice of 2-4 months olddisplay the same alterations previously described for olderanimals, in order to compare the results with those obtained forLID mice. Moreover, downstream signaling mediators that hadnot been studied were also analyzed. The second aim of thiswork was to evaluate possible mechanisms implicated in theimpaired insulin signaling. Mice received an insulin injection, theheart was removed after 5 min, and immunoblotting and ELISAassays of tissue extracts were performed. Insulin-inducedphosphorylation of the insulin receptor and downstream signalingmediators including IRS1, Akt, GSK3ß and AS160 weredecreased in the heart of GH-Tg and LID mice compared tonormal controls. This was associated with higher basalphosphorylation of MAPK p38 and Erk1/2 in LID mice, and only ofp38 in GH-Tg mice (p