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Trigonella foenum-graecum (fenugreek) seeds have been documented as a traditional plant treatment for diabetes. In the present study, the antidiabetic properties of a soluble dietary fibre (SDF) fraction of T. foenum-graecum were evaluated. Administration of SDF fraction (0·5 g/kg body weight) to normal, type 1 or type 2 diabetic rats significantly improved oral glucose tolerance. Total remaining unabsorbed sucrose in the gastrointestinal tract of non-diabetic and type 2 diabetic rats, following oral sucrose loading (2·5 g/kg body weight) was significantly increased by T. foenum-graecum (0·5 g/kg body weight). The SDF fraction suppressed the elevation of blood glucose after oral sucrose ingestion in both non-diabetic and type 2 diabetic rats. Intestinal disaccharidase activity and glucose absorption were decreased and gastrointestinal motility increased by the SDF fraction. Daily oral administration of SDF to type 2 diabetic rats for 28 d decreased serum glucose, increased liver glycogen content and enhanced total antioxidant status. Serum insulin and insulin secretion were not affected by the SDF fraction. Glucose transport in 3T3-L1 adipocytes and insulin action were increased by T. foenum-graecum. The present findings indicate that the SDF fraction of T. foenum-graecum seeds exerts antidiabetic effects mediated through inhibition of carbohydrate digestion and absorption, and enhancement of peripheral insulin action.

BACKGROUND AND PURPOSEG-protein coupled receptor (GPR)55 is a novel lipid sensing receptor activated by both cannabinoid endogenous ligands (endocannabinoids) and other non-cannabinoid lipid transmitters. This study assessed the effects of various GPR55 agonists on glucose homeostasis. EXPERIMENTAL APPROACHInsulin secretion and changes in intracellular Ca 2+ and cAMP in response to glucose and a range of GPR55 agonists [endogenous ligands (OEA, PEA), chemically synthetic cannabidiol (CBD) analogues (Abn-CBD, 0-1602), an analogue of rimonabant (AM-251) and antagonist (CBD)] were investigated in clonal BRIN-BD11 cells and mouse pancreatic islets. Cytotoxicity was assessed by LDH release, cellular localization by double-staining immunohistochemistry and in vivo effects assessed in mice. KEY RESULTSThe most potent and selective GPR55 agonist was the synthetic CBD analogue, Abn-CBD (pEC50 10.33), maximum stimulation of 67% at 10 −4 mol·L −1 (P < 0.001) in BRIN-BD11 cells. AM-251 (pEC50 7.0), OEA (pEC50 7.0), 0-1602 (pEC50 7.3) and PEA (pEC50 6.0) stimulated insulin secretion. Results were corroborated by islet studies, with no cytotoxic effects. Concentration-dependent insulin secretion by GPR55 agonists was glucose-sensitive and accompanied by elevations of [Ca 2+ ]i (P < 0.01-P < 0.001) and cAMP (P < 0.05-P < 0.01). GPR55 agonists exhibited insulinotropic and glucose lowering activity in vivo. GPR55 was expressed on BRIN-BD11 cells and confined to islet beta cells with no distribution on alpha cells. CONCLUSION AND IMPLICATIONSThese results demonstrate GPR55 is distributed in pancreatic beta cells and is a strong activator of insulin secretion, with glucose-lowering effects in vivo. Development of agents agonizing the GPR55 receptor may have therapeutic potential in the treatment of type 2 diabetes. AbbreviationsAbn-CBD, abnormal cannabidiol; CB1, Cannabinoid receptor 1; CB2, Cannabinoid receptor 2; CBD, Cannabidiol; GPR55, G-protein coupled receptor 55; OEA, oleoylethanolamide; PEA, palmitoylethanolamine BJP British Journal of Pharmacology

Ocimum sanctum leaves have previously been reported to reduce blood glucose when administered to rats and humans with diabetes. In the present study, the effects of ethanol extract and five partition fractions of O. sanctum leaves were studied on insulin secretion together with an evaluation of their mechanisms of action. The ethanol extract and each of the aqueous, butanol and ethylacetate fractions stimulated insulin secretion from perfused rat pancreas, isolated rat islets and a clonal rat -cell line in a concentration-dependent manner. The stimulatory effects of ethanol extract and each of these partition fractions were potentiated by glucose, isobutylmethylxanthine, tolbutamide and a depolarizing concentration of KCl.Inhibition of the secretory effect was observed with diazoxide, verapamil and Ca 2+ removal. In contrast, the stimulatory effects of the chloroform and hexane partition fractions were associated with decreased cell viability and were unaltered by diazoxide and verapamil. The ethanol extract and the five fractions increased intracellular Ca 2+ in clonal BRIN-BD11 cells, being partly attenuated by the addition of verapamil. These findings indicated that constituents of O. sanctum leaf extracts have stimulatory effects on physiological pathways of insulin secretion which may underlie its reported antidiabetic action.

These results indicate that GPR120 is expressed on pancreatic β-cells and that agonists at this receptor are potent insulin secretagogues with therapeutic potential for type 2 diabetes.