Insulin-like effect of pinitol

Abstract

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.

Figure 1

Structure of D-pinitol (1 D-3-O-methyl-chiroinositol).

Figure 2

Acute effect of D-pinitol (5, 10 and 100 mg kg⁻¹ p.o.) on plasma glucose in STZ-diabetic mice. Data are expressed as per cent change from time zero, mean±s.e.mean, n=10. Plasma glucose concentrations (mmol l⁻¹) at time zero were 25.5±2.6, 23.6±2.0, 18.9±2.4 and 25.3±1.3 for control and 5, 10 and 100 mg kg⁻¹ D-pinitol respectively ^*P<0.05, ^**P<0.02 versus time zero, †P<0.05 versus control at same time point.

Figure 3

Acute effect of D-pinitol (100 mg kg⁻¹ p.o.) on plasma glucose disappearance in response to insulin (1 u kg⁻¹ i.p. at 6 h) in STZ-diabetic mice. Plasma glucose disappearance (6 h to 6 h 40 min) was 1.3±0.2 and 1.1±0.2% per min for control and D-pinitol respectively. Values are mean±s.e.mean, n=6. ^*P<0.05 versus control at same time point.

Figure 4

Chronic effect of D-pinitol (100 mg kg⁻¹ i.p. twice daily) on plasma glucose in STZ-diabetic mice. Values are mean±s.e.mean, n=5. ^*P<0.05, ^**P<0.02 versus time zero and versus control at same time point.

Figure 5

2-deoxy-[³H]-glucose (2DG) uptake by L6 myotubes incubated for 24 h with insulin (10⁻⁹–10⁻⁵ M). Data are expressed as per cent control (no added insulin), mean±s.e.mean, n=18.

Figure 6

2-deoxy-[³H]-glucose (2DG) uptake by L6 myotubes incubated for 10 min, 4 h and 24 h with insulin (10⁻⁸ M) and/or D-pinitol (10⁻³ M). Data are expressed as per cent control (no addition of insulin or D-pinitol), mean±s.e.mean, n=18. ^*P<0.05 versus control at same time interval; †P<0.05 versus insulin alone.

Figure 7

2-deoxy-[³H]-glucose (2DG) uptake by L6 myotubes incubated for 4 h with insulin (10⁻⁸ M), D-pinitol (10⁻³ M) and/or LY294002 (10⁻⁵ M). C, control, I, insulin; P, D-pinitol; L, LY294002. Data are expressed as per cent control (no addition of insulin or D-pinitol), mean±s.e.mean, n=6. ^*P<0.05 versus control; +P<0.05 versus insulin; ‡P<0.05 versus D-pinitol.