Insulin signaling in the heart is impaired by growth hormone: a direct and early event

MUÑOZ, MARINA C.

JOURNAL OF MOLECULAR ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2022 vol. 69 p. 357 - 376

0952-5041

Growth hormone (GH) exerts major actions in cardiac growth and metabolism.Considering the important role of insulin in the heart and the well-established anti-insulineffects of GH, cardiac insulin resistance may play a role in the cardiopathology observedin acromegalic patients. As conditions of prolonged exposure to GH are associated witha concomitant increase of circulating GH, IGF1 and insulin levels, to dissect the directeffects of GH, in this study, we evaluated the activation of insulin signaling in the heartusing four different models: (i) transgenic mice overexpressing GH, with chronicallyelevated GH, IGF1 and insulin circulating levels; (ii) liver IGF1-deficient mice, withchronically elevated GH and insulin but decreased IGF1 circulating levels; (iii) mice treatedwith GH for a short period of time; (iv) primary culture of rat cardiomyocytes incubatedwith GH. Despite the differences in the development of cardiomegaly and in themetabolic alterations among the three experimental mouse models analyzed, exposureto GH was consistently associated with a decreased response to acute insulin stimulationin the heart at the receptor level and through the PI3K/AKT pathway. Moreover, a bluntedresponse to insulin stimulation of this signaling pathway was also observed in culturedcardiomyocytes of neonatal rats incubated with GH. Therefore, the key novel finding ofthis work is that impairment of insulin signaling in the heart is a direct and early eventobserved as a consequence of exposure to GH, which may play a major role in thedevelopment of cardiac pathology.