High-fat diet-induced insulin resistance does not increase plasma anandamide levels or potentiate anandamide insulinotropic effect in isolated canine islets

• Published in: PloS one 2015-04, Vol.10 (4), p.e0123558-e0123558
• Main Authors: Woolcott, Orison O, Richey, Joyce M, Kabir, Morvarid, Chow, Robert H, Iyer, Malini S, Kirkman, Erlinda L, Stefanovski, Darko, Lottati, Maya, Kim, Stella P, Harrison, L Nicole, Ionut, Viorica, Zheng, Dan, Hsu, Isabel R, Catalano, Karyn J, Chiu, Jenny D, Bradshaw, Heather, Wu, Qiang, Kolka, Cathryn M, Bergman, Richard N
• Format: Article
• Language: English
• Subjects: Abdominal Fat - drug effects; Abdominal Fat - metabolism; Analysis; Anandamide; Animals; Antimicrobial Cationic Peptides - biosynthesis; Arachidonic Acids - blood; Arachidonic Acids - genetics; Blood Glucose; Body Weight; Cannabinoid CB1 receptors; Cannabinoid CB2 receptors; Chromatography; Diet; Diet, High-Fat - adverse effects; Dogs; Endocannabinoids - blood; Endocannabinoids - genetics; Euthanasia; Gene expression; Glucagon; Glucose; Glycerol; High fat diet; Hormones; Humans; Hyperinsulinemia; In vitro methods and tests; In vivo methods and tests; Insulin; Insulin - metabolism; Insulin Resistance; Insulin secretion; Islets of Langerhans; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Kinases; Liquid chromatography; Magnetic resonance imaging; Mass spectrometry; Mass spectroscopy; Obesity; Obesity - blood; Obesity - pathology; Pancreas; Physicians; Physiological aspects; Polyunsaturated Alkamides - blood; Potentiation; Receptor, Cannabinoid, CB2 - biosynthesis; Receptors; Rodents; Secretion; Sensitivity; Sensitivity analysis; Somatostatin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0123558

Obesity has been associated with elevated plasma anandamide levels. In addition, anandamide has been shown to stimulate insulin secretion in vitro, suggesting that anandamide might be linked to hyperinsulinemia. To determine whether high-fat diet-induced insulin resistance increases anandamide levels and potentiates the insulinotropic effect of anandamide in isolated pancreatic islets. Dogs were fed a high-fat diet (n = 9) for 22 weeks. Abdominal fat depot was quantified by MRI. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp. Fasting plasma endocannabinoid levels were analyzed by liquid chromatography-mass spectrometry. All metabolic assessments were performed before and after fat diet regimen. At the end of the study, pancreatic islets were isolated prior to euthanasia to test the in vitro effect of anandamide on islet hormones. mRNA expression of cannabinoid receptors was determined in intact islets. The findings in vitro were compared with those from animals fed a control diet (n = 7). Prolonged fat feeding increased abdominal fat content by 81.3±21.6% (mean±S.E.M, P