Insulin-like effect of pinitol.
D-pinitol (3-O-methyl-chiroinositol), an active principle of the traditional antidiabetic plant Bougainvillea spectabilis, is claimed to exert insulin-like effects. This study investigates the effect of D-pinitol on glucose homeostasis in animal models of diabetes, and on glucose transport by cultured muscle cells. Plasma glucose concentrations were measured in normal, obese-diabetic (ob/ob) and streptozotocin (STZ)-diabetic mice after oral (p.o.) and intraperitoneal (i.p.) administration of D-pinitol. Glucose transport was measured in L6 rat muscle cells by 2-deoxyglucose (2DG) uptake. In STZ-diabetic mice, 100 mg kg(-1) p.o. D-pinitol acutely decreased the hyperglycaemia (by 22% at 6 h). A similar decrease in plasma glucose (by 21%) was observed after 100 mg kg(-1) i.p. D-pinitol. Insulin concentrations and the rate of insulin-induced (1 unit kg(-1) actrapid i.p.) glucose disappearance were not altered by 100 mg kg(-1) p.o. D-pinitol. Chronic administration of D-pinitol (100 mg kg(-1) i.p. twice daily for 11 days) to STZ-diabetic mice maintained a reduction in plasma glucose concentrations from about 14 to 10 mmol l(-1). In normal non-diabetic and severely insulin resistant ob/ob mice, 100 mg kg(-1) p.o. D-pinitol did not significantly affect plasma glucose or insulin during acute studies. Incubation of L6 muscle cells with D-pinitol (10(-3) M) increased basal 2DG uptake by 41% after 10 min and by 34% after 4 h. The effect of D-pinitol was inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. D-pinitol did not increase insulin-stimulated 2DG uptake by L6 cells. The data support the view that D-pinitol can exert an insulin-like effect to improve glycaemic control in hypoinsulinaemic STZ-diabetic mice. D-pinitol may act via a post-receptor pathway of insulin action affecting glucose uptake.
Bates
S H
SH
School of Life and Health Sciences, Aston University, Birmingham, USA.
Jones
R B
RB
Bailey
C J
CJ
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008820:Mice, Obese; D009025:Morpholines / Q000494:pharmacology; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000235:genetics; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013997:Time Factors
D001786:Blood Glucose; D002867:Chromones; D004791:Enzyme Inhibitors; D007328:Insulin; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C021730:pinitol; D007294:Inositol; D003847:Deoxyglucose