The insulin receptor family and protein kinase B (Akt) are activated in the heart by alkaline pH and ?1-adrenergic receptors

Insulin and insulin-like growth factor stimulate protein synthesis cardioprotection in the heart, acting through their receptors (INSRs, IGF1Rs) signalling via kinase B (PKB, also known as Akt). Protein is increased hearts perfused at alkaline pHo to same extent with insulin. Moreover, ?1-adrenergic receptor (?1-AR) agonists (e.g. phenylephrine) increase cardiomyocytes, activating PKB/Akt. In both cases, mechanisms are not understood. Our aim was determine if insulin receptor-related (INSRRs, activated kidney by pH) may account for effects of on cardiac synthesis, establish ?1-ARs signal family. Alkaline PKB/Akt degree adult male rat hearts. INSRRs were expressed and, immunoblotting phosphorylation (activation) INSRRs/INSRs/IGF1Rs, we established that INSRRs, together INSRs/IGF1Rs, pHo. The INSRR/INSR/IGF1R inhibitor, linsitinib, prevented activation pHo, indicating INSRRs/INSRs/IGF1Rs required. Activation cardiomyocytes ?1-AR inhibited linsitinib. Furthermore, linsitinib cardiomyocyte hypertrophy induced cultured cells, reduced initial adaptation (24 h) phenylephrine vivo (assessed echocardiography) fibrosis over 4 days. We conclude heart family provide a potent system promoting cardioprotection. this required adaptive ?1-ARs.