Antidiabetic and Cardioprotective Effects of Pharmacological Inhibition of GRK2 in db/db Mice

International Journal of Molecular Sciences

Enrico Coscioni¹  Ersilia Cipolletta²  Jessica Gambardella²  Antonella Fiordelisi²  Eugenio Di Vaia²  Daniela Sorriento²  Guido Iaccarino²  Bruno Trimarco²  Carmine Del Giudice²  Michele Ciccarelli³  Marina Sala⁴  Pietro Campiglia⁴ 

[1] AOU San Giovanni di Dio e Ruggi d’Aragona, 84131 Salerno, Italy;Department of Advanced Biomedical Sciences, “Federico II” University of Naples, 80131 Napoli, Italy;Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy;Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy;

关键词: kinase;    signaling;    insulin sensitivity;    heart failure;    kinase inhibitor;   

DOI  :  10.3390/ijms20061492

来源: DOAJ

【 摘 要 】

Despite the availability of several therapies for the management of blood glucose in diabetic patients, most of the treatments do not show benefits on diabetic cardiomyopathy, while others even favor the progression of the disease. New pharmacological targets are needed that might help the management of diabetes and its cardiovascular complications at the same time. GRK2 appears a promising target, given its established role in insulin resistance and in systolic heart failure. Using a custom peptide inhibitor of GRK2, we assessed in vitro in L6 myoblasts the effects of GRK2 inhibition on glucose extraction and insulin signaling. Afterwards, we treated diabetic male mice (db/db) for 2 weeks. Glucose tolerance (IGTT) and insulin sensitivity (ITT) were ameliorated, as was skeletal muscle glucose uptake and insulin signaling. In the heart, at the same time, the GRK2 inhibitor ameliorated inflammatory and cytokine responses, reduced oxidative stress, and corrected patterns of fetal gene expression, typical of diabetic cardiomyopathy. GRK2 inhibition represents a promising therapeutic target for diabetes and its cardiovascular complications.

【 授权许可】

Unknown