Insulin signaling in the heart is directly and early impaired by growth 4 hormone

MARINA C MUÑOZ; VERÓNICA G PIAZZA; VALERIA BURGHI; JORGE F GIANI; CAROLINA S MARTINEZ; NADIA S CICCONI; NADIA V MUIA; YIMIN FANG; SERGIO LAVANDERO; ANA I SOTELO; ANDRZEJ BARTKE; PATRICIA A PENNISI; FERNANDO P DOMINICI; JOHANNA G MIQUET

JOURNAL OF MOLECULAR ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2022

0952-5041

Growth hormone (GH) exerts major actions in cardiac growth and metabolism. Considering40 the important role of insulin in the heart and the well-established anti-insulin effects of GH,41 cardiac insulin resistance may play a role in the cardiopathology observed in acromegalic42 patients. As conditions of prolonged exposure to GH are associated with a concomitant increase43 of circulating GH, IGF-1 and insulin levels, to dissect the direct effects of GH, in this study we44 evaluated the activation of insulin signaling in the heart using four different models: 1)45 transgenic mice overexpressing GH, with chronically elevated GH, IGF-1 and insulin circulating46 levels, 2) liver IGF-1-deficient mice, with chronically elevated GH and insulin but decreased IGF47 1 circulating levels, 3) mice treated with GH for a short period of time, and 4) primary culture of48 rat cardiomyocytes incubated with GH. Despite the differences in the development of49 cardiomegaly and in the metabolic alterations among the three experimental mouse models50 analysed, exposure to GH was consistently associated with a decreased response to acute insulin51 stimulation in the heart at the receptor level and through the PI3K/Akt pathway. Moreover, a52 blunted response to insulin stimulation of this signaling pathway was also observed in cultured53 cardiomyocytes of neonatal rats incubated with GH. Therefore, the key novel finding of this work54 is that impairment of insulin signaling in the heart is a direct and early event observed as a55 consequence of exposure to GH, which may play a major role in the development of cardiac56 pathology.