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Despite considerable progress in the management of diabetes mellitus with synthetic drugs, the search for indigenous natural antidiabetic agents is ongoing. The plant kingdom offers a wide field to search for effective oral hypoglycemics. More than 400 species have been reported to exhibit hypoglycemic effects, but only a few have been investigated. [1][2][3][4][5] The leaf of Banaba (Lagerstroemia speciosa L.) has been used as a traditional Oriental medicine to treat diabetes (polyuria and polydipsia). It contains polyphenol compounds and corosolic acid (CA) (Fig. 1).6) In a previous study, it was reported that polyphenol compounds have antidiabetic effects.7) We found a new antidiabetic compound, CA of Banaba leaf, for single oral administration. 8) However, there is no experimental evidence detailing improved hyperglycemia after repeated administration. In the present study, we examined the antidiabetic effects of CA in KK-Ay diabetic mice, an animal model of type 2 diabetes. MATERIALS AND METHODSMaterials CA was donated by Use Techno Corporation Co. Ltd. (Kyoto, Japan). CA was stored at room temperature until use. For oral administration, CA 0.4, 2 and 10 mg/kg was suspended in distilled water 20 ml. For subcutaneous administration, insulin 0.5 U/kg was dissolved in saline 10 ml.Animals and Treatments KK-Ay strain male mice (6 weeks old, weighing 39-43 g) (Clea, Tokyo, Japan) with a blood glucose level greater than 300 mg/dl and considered to be diabetic were used. The mice were housed in an air-conditioned room at 22Ϯ2°C with a 12-h light and 12-h dark cycle. The animals were kept in the experimental animal room for 7 d with free access to food and water. Blood samples were withdrawn from the cavernous sinus with a capillary for glucose determinations. The experiments were started between 10:00 and 11:00 am.Effects of a Single Dose of CA on Blood Glucose Levels in KK-Ay Mice CA (0.4, 2, 10 mg/kg) dissolved in 20 ml of distilled water was administered orally to the mice. The control group received an equal volume (20 ml/kg) of distilled water. Blood samples were taken for glucose determination 2, 4, and 7 h later. This experiment was performed under nonfasting conditions.Effects of 2-Week Repeated Administration of CA on Blood Glucose Levels in KK-Ay Mice CA 2 mg/kg suspended in 20 ml of distilled water was administered orally once a day for 2 weeks to the mice. The control group received an equal volume (20 ml/kg) of distilled water. Blood samples were taken for glucose determination every week. This experiment was performed under nonfasting conditions. Insulin Tolerance Test An insulin tolerance test was performed at the end of the repeated administration period. After overnight fasting, an insulin solution 0.5 U/kg was injected subcutaneously into the mice and blood samples were obtained for glucose determinations 0, 30, 60, and 120 min later.Determination of Blood Glucose and Insulin Levels Blood glucose levels in both normal and diabetic animals were determined using the glucose oxidase method 9) and pl...

The effect of corosolic acid (CA) on blood glucose was studied in KK-Ay mice, an animal model of type 2 diabetes. CA (10 mg/kg) reduced the blood glucose (pϽ0.05) of KK-Ay mice 4 h after single oral administration when compared with the control group. However, CA did not change the plasma insulin. The muscle facilitative glucose transporter isoform 4 (GLUT4) translocation from low-density microsomal membrane to plasma membrane was significantly increased in the orally CA-treated mice when compared with that of the controls (pϽ0.05). These results suggest that the hypoglycemic effect of CA is derived, at least in part, from an increase in GLUT4 translocation in muscle. Therefore, it may be that CA has beneficial effects on hyperglycemia in type 2 diabetes.

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