Transient gain of function of cannabinoid CB1 receptors in the control of frontocortical glucose consumption in a rat model of Type-1 diabetes

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Pedro, JR (Author) Other; Moura, LIF (Author) Other; Valerio Fernandes, A (Author) Other; Baptista, FI (Author) Other; Gaspar, JM (Author) Other; Pinheiro, BS (Author) Other; Lemos, C (Author) Other; Kaufmann, FN (Author) Other; Morgado, C (Author) Other; da Silva Santos, CS (Author) Other; Isaura Tavares (Author) FMUP; Ferreira, SG (Author) Other; Carvalho, E (Author) Other; Ambrosio, AF (Author) Other; Cunha, RA (Author) Other; Duarte, JMN (Author) Other; Kofalvi, A (Author) Other

Journal

Title: Brain Research Bulletin

Vol. 161

Pages: 106-115

ISSN: 0361-9230

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00S-5VH

DOI: 10.1016/j.brainresbull.2020.05.004

Abstract (EN): Here we aimed to unify some previous controversial reports on changes in both cannabinoid CB1 receptor (CB1R) expression and glucose metabolism in the forebrain of rodent models of diabetes. We determined how glucose metabolism and its modulation by CB1R 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 CB1R 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 CB1R agonists, WIN55212 - 2 (500 nM) and the CB1R-selective agonist, ACEA (3 mu M) while it was exacerbated by the CB1R-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 GSK alpha and GSK beta levels showed different profiles 2 and 8 weeks after T1D induction in the frontal cortex. Altogether, the biphasic response in frontocortical CB1R density within a month after T1D induction resolves previous controversial reports on forebrain CB1R levels in T1D rodent models. Furthermore, this study also hints that cannabinoids may be useful to alleviate impaired glucoregulation in the diabetic cortex.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10