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Open AccessArticle

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

1
Department of Advanced Biomedical Sciences, “Federico II” University of Naples, 80131 Napoli, Italy
2
Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy
3
Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy
4
AOU San Giovanni di Dio e Ruggi d’Aragona, 84131 Salerno, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1492; https://doi.org/10.3390/ijms20061492
Received: 27 February 2019 / Revised: 17 March 2019 / Accepted: 20 March 2019 / Published: 25 March 2019
(This article belongs to the Special Issue Mechanisms of Inflammation in Degenerative Cardiovascular Conditions)
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. View Full-Text
Keywords: kinase; signaling; insulin sensitivity; heart failure; kinase inhibitor kinase; signaling; insulin sensitivity; heart failure; kinase inhibitor
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MDPI and ACS Style

Cipolletta, E.; Gambardella, J.; Fiordelisi, A.; Del Giudice, C.; Di Vaia, E.; Ciccarelli, M.; Sala, M.; Campiglia, P.; Coscioni, E.; Trimarco, B.; Sorriento, D.; Iaccarino, G. Antidiabetic and Cardioprotective Effects of Pharmacological Inhibition of GRK2 in db/db Mice. Int. J. Mol. Sci. 2019, 20, 1492. https://doi.org/10.3390/ijms20061492

AMA Style

Cipolletta E, Gambardella J, Fiordelisi A, Del Giudice C, Di Vaia E, Ciccarelli M, Sala M, Campiglia P, Coscioni E, Trimarco B, Sorriento D, Iaccarino G. Antidiabetic and Cardioprotective Effects of Pharmacological Inhibition of GRK2 in db/db Mice. International Journal of Molecular Sciences. 2019; 20(6):1492. https://doi.org/10.3390/ijms20061492

Chicago/Turabian Style

Cipolletta, Ersilia; Gambardella, Jessica; Fiordelisi, Antonella; Del Giudice, Carmine; Di Vaia, Eugenio; Ciccarelli, Michele; Sala, Marina; Campiglia, Pietro; Coscioni, Enrico; Trimarco, Bruno; Sorriento, Daniela; Iaccarino, Guido. 2019. "Antidiabetic and Cardioprotective Effects of Pharmacological Inhibition of GRK2 in db/db Mice" Int. J. Mol. Sci. 20, no. 6: 1492. https://doi.org/10.3390/ijms20061492

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