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ludc web

Joao Duarte

Research team manager

ludc web

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

Author

  • Joana Reis Pedro
  • Liane I.F. Moura
  • Ângela Valério-Fernandes
  • Filipa I. Baptista
  • Joana M. Gaspar
  • Bárbara S. Pinheiro
  • Cristina Lemos
  • Fernanda Neutzling Kaufmann
  • Carla Morgado
  • Carla S.da Silva-Santos
  • Isaura Tavares
  • Samira G. Ferreira
  • Eugénia Carvalho
  • António F. Ambrósio
  • Rodrigo A. Cunha
  • João M.N. Duarte
  • Attila Köfalvi

Summary, in English

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 μM) while it was exacerbated by the CB1R-selective antagonist, O-2050 (500 nM). These results suggest a gain-of-function for the cerebrocortical CB1Rs 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 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.

Department/s

  • WCMM-Wallenberg Centre for Molecular Medicine
  • Diabetes and Brain Function
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2020

Language

English

Pages

106-115

Publication/Series

Brain Research Bulletin

Volume

161

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Keywords

  • Cannabinoid CBreceptor
  • Cerebral glucose metabolism
  • Frontal cortex
  • Goto-Kakizaki rat
  • type-1 diabetes
  • Wistar rat

Status

Published

Research group

  • Diabetes and Brain Function

ISBN/ISSN/Other

  • ISSN: 0361-9230