Transient gain of function of cannabinoid CB 1 receptors in the control of frontocortical glucose consumption in a rat model of Type-1 diabetes.

Autor: Pedro JR; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal., Moura LIF; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal., Valério-Fernandes Â; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal., Baptista FI; Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal., Gaspar JM; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal., Pinheiro BS; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal., Lemos C; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal., Kaufmann FN; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal., Morgado C; Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal., Silva-Santos CSD; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal., Tavares I; Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal; I3S Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal., Ferreira SG; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal., Carvalho E; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal; The Portuguese Diabetes Association (APDP), Lisbon, Portugal; Arkansas Children's Research Institute, and Department of Geriatrics, University of Arkansas for Medical Sciences, Arkansas 72205, United States., Ambrósio AF; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; Association for Innovation and Biomedical Research on Light and Image (AIBILI), 3000-548 Coimbra, Portugal., Cunha RA; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal., Duarte JMN; Department of Experimental Medical Science, Faculty of Medicine, Lund University, Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden., Köfalvi A; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal. Electronic address: akofalvi@uc.pt.
Jazyk: angličtina
Zdroj: Brain research bulletin [Brain Res Bull] 2020 Aug; Vol. 161, pp. 106-115. Date of Electronic Publication: 2020 May 16.
DOI: 10.1016/j.brainresbull.2020.05.004
Abstrakt: Here we aimed to unify some previous controversial reports on changes in both cannabinoid CB 1 receptor (CB 1 R) expression and glucose metabolism in the forebrain of rodent models of diabetes. We determined how glucose metabolism and its modulation by CB 1 R ligands evolve in the frontal cortex of young adult male Wistar rats, in the first 8 weeks of streptozotocin-induced type-1 diabetes (T1D). We report that frontocortical CB 1 R protein density was biphasically altered in the first month of T1D, which was accompanied with a reduction of resting glucose uptake ex vivo in acute frontocortical slices that was normalized after eight weeks in T1D. This early reduction of glucose uptake in slices was also restored by ex vivo treatment with both the non-selective CB 1 R agonists, WIN55212-2 (500 nM) and the CB 1 R-selective agonist, ACEA (3 μM) while it was exacerbated by the CB 1 R-selective antagonist, O-2050 (500 nM). These results suggest a gain-of-function for the cerebrocortical CB 1 Rs in the control of glucose uptake in diabetes. Although insulin and IGF-1 receptor protein densities remained unaffected, phosphorylated GSKα and GSKβ levels showed different profiles 2 and 8 weeks after T1D induction in the frontal cortex. Altogether, the biphasic response in frontocortical CB 1 R density within a month after T1D induction resolves previous controversial reports on forebrain CB 1 R levels in T1D rodent models. Furthermore, this study also hints that cannabinoids may be useful to alleviate impaired glucoregulation in the diabetic cortex.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The funding agencies had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: