Table 2.
Effects of endocannabinoid system and cannabinoids on carbohydrate and lipid metabolism and a relationship with insulin resistance and type 2 diabetes mellitus. Analysis from references. Original and review articles discussing CB receptor-dependent methods (KO mice, agonists, antagonists) are emphasized. CBR, cannabinoid receptors, CB1R and CB2R, cannabinoid receptors type 1 and 2, KO, knockout, 2-AG, 2-arachidonoylglycerol, THC, tetrahydrocannabinol, AEA, anandamide, ACEA, arachidonyl-2-chloroethyl amide, IR, insulin resistance, AKT, protein kinase B, GLUT2, glucose transporter 2, HFD, high-fat diet.
| Ref. | Article Type | Animal Model | Diet | Receptors, Agonist/Antagonist | Short Summary | Studied Mechanism and Disease |
|---|---|---|---|---|---|---|
| Després et al., 2005 [69] | Clinical study | CBR antagonist rimonabant | Rimonabant treatment decreases insulin levels and improves glucose tolerance in obese patients. | Obesity, IR | ||
| Kim et al., 2011 [76] | Cells, animal study | Isolated human/ mouse islets, beta cell line, db/db and CB1R-KO mice |
CBR agonists AEA, 2-AG, CBR antagonists AM251, AM630 | Inhibition of CB1Rs enhances pancreatic beta cell signaling and proliferation in isolated islets, and also improves glucose tolerance and insulin sensitivity (in db/db mice). | IR | |
| Liu et al., 2012 [77] | Cells, animal study | CB1R-KO mice, human/mouse hepatocytes | high-fat diet | CBR agonist anandamide | HFD induces hepatic IR in wild-type but not in CB1R-KO mice. CB1R activation contributes to diet-induced IR via hepatic CB1R-mediated inhibition of insulin signaling. | Obesity, IR |
| Shin et al., 2018 [78] | Cell/animal study | CB1R-KO mice, mouse beta cell line, human islet | CBR agonist 2-AG, ACEA, WIN55212, CBR antagonist AM251 | CB1R agonists diminishes insulin secretion in β cell line and islets, whereas silencing CB1Rs in β cells increases expression of proinsulin, glucokinase and GLUT2 glucose transporter, which is also observed in CB1R-KO mice. | IR, type 2 diabetes | |
| Motaghedi and McGraw, 2008 [79] | Cells | Adipocytes | CBR agonist 2-AG, CBR antagonist SR141716 | Activation of CB1R by 2-AG promotes insulin sensitivity by increasing insulin-stimulated AKT phosphorylation in adipocytes, which is attenuated by CB1R antagonist. | IR | |
| Hirsch and Tam, 2019 [3] | Review (animal/clinical studies) | CB1R antagonists | CB1R blockade decreases food intake and body weight, and ameliorates obesity, type 2 diabetes, fatty liver, and IR in animals. It also decreases body weight and improves glucose homeostasis in obese individuals. | Obesity, metabolic syndrome, type 2 diabetes | ||
| Di Marzo, 2008 [15] | Review (animal/clinical studies) | CB1R-KO mice, obese Zucker rats | CB1R, CB2R, TRPV1; CBR agonists (AEA, 2-AG), CBR antagonists (rimonabant, taranabant) | CB1R antagonists reduce hyperglycemia and dyslipidemia, improving insulin resistance and glucose tolerance in obesity and type 2 diabetes. | Obesity and type 2 diabetes | |
| Nagappan, Shin, and Jung, 2019 [52] | Review (animal/clinical studies) | CB1R agonists/overexpression CB1R antagonists |
CB1R activation modulates insulin signaling pathway and leads to insulin resistance. | Obesity, IR, type 2 diabetes |