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Article

CXCR1/2 Inhibitor Ladarixin Ameliorates the Insulin Resistance of 3T3-L1 Adipocytes by Inhibiting Inflammation and Improving Insulin Signaling

1
Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
2
Dompè Farmaceutici SpA, Via Campo di Pile, 67100 L’Aquila, Italy
3
Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology, Temple University, Philadelphia, PA 19122, USA
*
Authors to whom correspondence should be addressed.
Authors equally contributed to this work.
Academic Editors: Kai Sun and Jae Bum Kim
Cells 2021, 10(9), 2324; https://doi.org/10.3390/cells10092324
Received: 10 August 2021 / Revised: 25 August 2021 / Accepted: 29 August 2021 / Published: 6 September 2021
(This article belongs to the Special Issue Adipocytes and Metabolic Health - Second Edition)
Type 2 diabetes mellitus is a severe public health issue worldwide. It displays a harmful effect on different organs as the eyes, kidneys and neural cells due to insulin resistance and high blood glucose concentrations. To date, the available treatments for this disorder remain limited. Several reports have correlated obesity with type 2 diabetes. Mainly, dysfunctional adipocytes and the regulation of high secretion of inflammatory cytokines are the crucial links between obesity and insulin resistance. Several clinical and epidemiological studies have also correlated the onset of type 2 diabetes with inflammation, which is now indicated as a new target for type 2 diabetes treatment. Thus, it appears essential to discover new drugs able to inhibit the secretion of proinflammatory adipocytokines in type 2 diabetes. Adipocytes produce inflammatory cytokines in response to inflammation or high glucose levels. Once activated by a specific ligand, CXCR1 and CXCR2 mediate some cytokines’ effects by activating an intracellular signal cascade once activated by a specific ligand. Therefore, it is conceivable to hypothesize that a specific antagonist of these receptors may ameliorate type 2 diabetes and glucose metabolism. Herein, differentiated 3T3-L1-adipocytes were subjected to high glucose or inflammatory conditions or the combination of both and then treated with ladarixin, a CXCR1/2 inhibitor. The results obtained point towards the positive regulation by ladarixin on insulin sensitivity, glucose transporters GLUT1 and GLUT4, cytokine proteome profile and lipid metabolism, thus suggesting ladarixin as a potentially helpful treatment in type 2 diabetes mellitus and obesity. View Full-Text
Keywords: diabetes; obesity; inflammation; glucose uptake; insulin resistance; pharmacological approach diabetes; obesity; inflammation; glucose uptake; insulin resistance; pharmacological approach
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MDPI and ACS Style

Castelli, V.; Brandolini, L.; d’Angelo, M.; Giorgio, C.; Alfonsetti, M.; Cocchiaro, P.; Lombardi, F.; Cimini, A.; Allegretti, M. CXCR1/2 Inhibitor Ladarixin Ameliorates the Insulin Resistance of 3T3-L1 Adipocytes by Inhibiting Inflammation and Improving Insulin Signaling. Cells 2021, 10, 2324. https://doi.org/10.3390/cells10092324

AMA Style

Castelli V, Brandolini L, d’Angelo M, Giorgio C, Alfonsetti M, Cocchiaro P, Lombardi F, Cimini A, Allegretti M. CXCR1/2 Inhibitor Ladarixin Ameliorates the Insulin Resistance of 3T3-L1 Adipocytes by Inhibiting Inflammation and Improving Insulin Signaling. Cells. 2021; 10(9):2324. https://doi.org/10.3390/cells10092324

Chicago/Turabian Style

Castelli, Vanessa, Laura Brandolini, Michele d’Angelo, Cristina Giorgio, Margherita Alfonsetti, Pasquale Cocchiaro, Francesca Lombardi, Annamaria Cimini, and Marcello Allegretti. 2021. "CXCR1/2 Inhibitor Ladarixin Ameliorates the Insulin Resistance of 3T3-L1 Adipocytes by Inhibiting Inflammation and Improving Insulin Signaling" Cells 10, no. 9: 2324. https://doi.org/10.3390/cells10092324

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