Flatt, Peter R

Lafferty, Ryan A

McCloskey, Andrew G

McKillop, Aine M

Miskelly, Michael G

English

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 (0.1µmol/kg BW) monotherapy and in combination with sitagliptin (50mg/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&lt;0.01 - p&lt;0.001) and enhanced circulating insulin concentrations by 23-31% (p&lt;0.001). Abn-CBD alone and with sitagliptin reduced bodyweight by 9-10% (p&lt;0.05). After 21-days, Abn-CBD in combination with sitagliptin (44%; p&lt;0.01) improved glucose tolerance, whilst enhancing insulin sensitivity by 79% (p&lt;0.01). Abn-CBD increased islet area (86%; p&lt;0.05), beta cell mass (p&lt;0.05) and beta cell proliferation (164%; p&lt;0.001), whilst in combination with sitagliptin islet area was decreased (50%; p&lt;0.01). Abn-CBD alone, in combination with sitagliptin or sitagliptin alone decreased triglycerides by 34-65% (p&lt;0.001) and total cholesterol concentrations by 15-25% (p&lt;0.001). In addition, Abn-CBD in combination with sitagliptin reduced fat mass by 19% (p&lt;0.05) and reduced CRP concentrations (39%; p&lt;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.</p

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

https://pure.ulster.ac.uk/files/111766244/1_s2.0_S0006295222004944_main.pdf

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

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