دورية أكاديمية
أعرض في EDS

Antidiabetic actions of GPR55 agonist Abn-CBD and sitagliptin in obese-diabetic high fat fed mice.

التفاصيل البيبلوغرافية
العنوان: Antidiabetic actions of GPR55 agonist Abn-CBD and sitagliptin in obese-diabetic high fat fed mice.
المؤلفون: McCloskey AG; School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, BT52 1SA, Northern Ireland, U.K; Health and Biomedical Research Centre (HEAL), Atlantic Technological University, ATU Sligo, Ash Lane, Sligo, F91 YW50, Ireland., Miskelly MG; School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, BT52 1SA, Northern Ireland, U.K., Lafferty RA; School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, BT52 1SA, Northern Ireland, U.K., Flatt PR; School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, BT52 1SA, Northern Ireland, U.K., McKillop AM; School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, BT52 1SA, Northern Ireland, U.K. Electronic address: am.mckillop@ulster.ac.uk.
المصدر: Biochemical pharmacology [Biochem Pharmacol] 2023 Feb; Vol. 208, pp. 115398. Date of Electronic Publication: 2022 Dec 26.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Elsevier Science
Original Publication: Oxford, New York [etc.] Paragamon Press.
مواضيع طبية MeSH: Insulin Resistance* , Diabetes Mellitus, Experimental*/drug therapy , Diabetes Mellitus, Experimental*/metabolism, Mice ; Animals ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Sitagliptin Phosphate/pharmacology ; Sitagliptin Phosphate/therapeutic use ; Receptors, Cannabinoid/metabolism ; Blood Glucose/metabolism ; Insulin/metabolism ; Obesity/drug therapy
مستخلص: GPR55 has been recognized as a novel anti-diabetic target exerting positive effects on beta cell function and mass. This study evaluated the metabolic actions and therapeutic efficacy of GPR55 agonist abnormal cannabidiol (Abn-CBD) administered alone and in combination with sitagliptin in diet-induced obese-diabetic mice. Chronic effects of 21-day oral administration of Abn-CBD (0.1 µmol/kg BW) monotherapy and in combination with sitagliptin (50 mg/kg BW) were assessed in obese-diabetic HFF mice (n = 8). Assessments of plasma glucose, circulating insulin, DPP-IV activity, CRP, amylase, lipids, body weight and food intake were undertaken. Glucose tolerance, insulin sensitivity, DEXA scanning and islet morphology analysis were performed at 21-days. Sitagliptin, Abn-CBD alone and in combination with sitagliptin attenuated plasma glucose by 37-53 % (p < 0.01 - p < 0.001) and enhanced circulating insulin concentrations by 23-31 % (p < 0.001). Abn-CBD alone and with sitagliptin reduced bodyweight by 9-10 % (p < 0.05). After 21-days, Abn-CBD in combination with sitagliptin (44 %; p < 0.01) improved glucose tolerance, whilst enhancing insulin sensitivity by 79 % (p < 0.01). Abn-CBD increased islet area (86 %; p < 0.05), beta cell mass (p < 0.05) and beta cell proliferation (164 %; p < 0.001), whilst in combination with sitagliptin islet area was decreased (50 %; p < 0.01). Abn-CBD alone, in combination with sitagliptin or sitagliptin alone decreased triglycerides by 34-65 % (p < 0.001) and total cholesterol concentrations by 15-25 % (p < 0.001). In addition, Abn-CBD in combination with sitagliptin reduced fat mass by 19 % (p < 0.05) and reduced CRP concentrations (39 %; p < 0.05). These findings advocate Abn-CBD monotherapy and in combination with sitagliptin as a novel and effective approach for bodyweight control and the treatment of glucose intolerance and dyslipidaemia in type-2-diabetes.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022. Published by Elsevier Inc.)
معلومات مُعتمدة: United Kingdom DUK_ Diabetes UK
فهرسة مساهمة: Keywords: Abnormal Cannabidiol; Beta Cell; DPP-IV Inhibition; Diabetes; GPR55; Incretins
المشرفين على المادة: 0 (Hypoglycemic Agents)
TS63EW8X6F (Sitagliptin Phosphate)
0 (4-(3-3,4-p-menthadien-(1,8)-yl)olivetol)
0 (Receptors, Cannabinoid)
0 (Blood Glucose)
0 (Insulin)
0 (GPR55 protein, mouse)
تواريخ الأحداث: Date Created: 20221229 Date Completed: 20230127 Latest Revision: 20230209
رمز التحديث: 20230209
DOI: 10.1016/j.bcp.2022.115398
PMID: 36581052
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-2968
DOI:10.1016/j.bcp.2022.115398