title: Role of the endocannabinoid system in diabetes and diabetic complications.
abstract: Increasing evidence suggests that an overactive endocannabinoid system (ECS) may contribute to the development of diabetes by promoting energy intake and storage, impairing both glucose and lipid metabolism, by exerting pro-apoptotic effects in pancreatic beta cells and by facilitating inflammation in pancreatic islets. Furthermore, hyperglycaemia associated with diabetes has also been implicated in triggering perturbations of the ECS amplifying the pathological processes mentioned above, eventually culminating in a vicious circle. Compelling evidence from preclinical studies indicates that the ECS also influences diabetes-induced oxidative stress, inflammation, fibrosis and subsequent tissue injury in target organs for diabetic complications. In this review, we provide an update on the contribution of the ECS to the pathogenesis of diabetes and diabetic microvascular (retinopathy, nephropathy and neuropathy) and cardiovascular complications. The therapeutic potential of targeting the ECS is also discussed.
  
  
  BACKGROUND
  This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.
authors.affiliation: Laboratory of Diabetic Nephropathy, Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Gruden
authors.affiliation: Laboratory of Diabetic Nephropathy, Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Barutta
authors.affiliation: Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Kunos
authors.affiliation: Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Pacher
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002185:Cannabidiol / Q000627:therapeutic use; D002908:Chronic Disease; D048909:Diabetes Complications / Q000378:metabolism* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000517:prevention & control; D063388:Endocannabinoids / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D002185:Cannabidiol