Corosolic Acid Induces GLUT4 Translocation in Genetically Type 2 Diabetic Mice

The leaf of Banaba (Lagerstroemia speciosa LINN.) has NaHCO3 (pH 7.0)) at 4°C. Subfractionation of the muscle been used as an Oriental traditional medicine to treat dia- membrane was as described by Baron et al.,15) whose procebetes (polyuria and polydipsia) in the Philippines.Banaba dure was modified from that of Klip et al,The muscle leaf has been reported to have an antidiabetic effect.We found a new antidiabetic compound, corosolic acid, of Banaba leaf. Therefore, we examined the hypoglycemic effect of corosolic acid in type 2 diabetes using an animal model.

Effect of CA on Blood Glucose and Insulin in KK-Ay Mice The mean blood glucose levels in KK-Ay mice after oral administration of CA are shown in Fig. 2. CA (10 mg/kg) decreased the blood glucose level 4h after the oral administration when compared with the controls (p0.05)ob/ob mice20) and KK mice,21) had hyperinsulinemia as a result of insulin resistance. CA decreased the blood glucose of KK-Ay mice. CA did not affect the blood glucose of normal mice (data not shown). These findings indicate that CA is useful for type 2 diabetes. It may be that CA has a beneficial effect on hyperglycemia in type 2 diabetics.
Furthermore, we examined the effect of CA on GLUT4 glucose transporter in mouse muscle, since it has been reported that GLUT4 plays a crucial role in the muscle process of glucose uptake. It is known that, in response to insulin secretion, GLUT4 translocates from a low-density microsome membrane (LDM) to the plasma membrane (PM) fraction, permitting the entry of glucose into myocytes. In a preliminary study, we examined dose-dependence (0.4, 2, 10mg/kg) after treatment with CA, and found that the most effective dose was 10mg/kg (data not shown). Therefore, we studied the effect of a glucose transporter of CA at the dosage of 10 mg/kg body weight. CA increased the PM GLUT4 protein content of muscle in KK-Ay mice. It is known that GLUT4 and GLUT1 are present in skeletal muscle. However, CA did not affect the GLUT1 protein content in skeletal muscle (data not shown).
From these findings, it is very likely that the hypoglycemic effect of CA is derived, at least in part, from increased glucose transport, presumably because of the GLUT4 translocation mechanism, it is possible to activate AMP-protein kinase.
Typical therapeutic agents to stimulate insulin secretion (such as a glibenclamide) have been used for type 2 diabetic patients. However, in this study, CA did not affect the insulin level of KK-Ay mice, suggesting that the antidiabetic mechanism of CA is different from a glibenclamide.
The constituents of Banaba have been investigated chemically with some tannins.As is a well-known Tannin action, it is possible to inhibit glucose uptake in the small intestine. However, the structure of CA is different from tannins, as shown in Fig. 1.
Further investigations will be needed to elucidate the mechanism of these effects. These results suggest the validity of the clinical use of Banaba leaf in the treatment of diabetes mellitus.

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