title: Endocannabinoid regulation of β-cell functions: implications for glycaemic control and diabetes.
abstract: Visceral obesity is a major risk factor for the development of insulin resistance which can progress to overt type 2 diabetes (T2D) with loss of β-cell function and, ultimately, loss of β-cells. Insulin secretion by β-cells of the pancreatic islets is tightly coupled to blood glucose concentration and modulated by a large number of blood-borne or locally released mediators, including endocannabinoids. Obesity and its complications, including T2D, are associated with increased activity of the endocannabinoid/CB1 receptor (CB1 R) system, as indicated by the therapeutic effects of CB1 R antagonists. Similar beneficial effects of CB1 R antagonists with limited brain penetrance indicate the important role of CB1 R in peripheral tissues, including the endocrine pancreas. Pancreatic β-cells express all of the components of the endocannabinoid system, and endocannabinoids modulate their function via both autocrine and paracrine mechanisms, which influence basal and glucose-induced insulin secretion and also affect β-cell proliferation and survival. The present brief review will survey available information on the modulation of these processes by endocannabinoids and their receptors, with an attempt to assess the contribution of such effects to glycaemic control in T2D and insulin resistance.
authors.affiliation: Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jourdan
authors.affiliation: Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: G
authors.initials: G
authors.lastname: Godlewski
authors.affiliation: Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: G
authors.initials: G
authors.lastname: Kunos
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002188:Cannabis / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D063388:Endocannabinoids / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology
chemical_list: D001786:Blood Glucose; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1
keywords: diabetes; endocannabinoids; inflammation; pancreas