Postprandial hypoglycemic effect of mulberry leaf in Goto-Kakizaki rats and counterpart control Wistar rats

Abstract

Postprandial hypoglycemic effect of mulberry leaf (Morus alba L.) was compared in two animal models: Goto-Kakizaki (GK) rats, a spontaneous non-obese animal model for type II diabetes, and their counterpart control Wistar rats. First, the effect of a single oral administration of mulberry leaf aqueous extract (MLE) on postprandial glucose responses was determined using maltose or glucose as substrate. With maltose-loading, MLE reduced peak responses of blood glucose significantly in both GK and Wistar rats (P < 0.05), supporting the inhibition of alpha-glucosidase by MLE in the small intestine. With glucose-loading, MLE also significantly reduced blood glucose concentrations, measured at 30 min, in both animal models (P < 0.01), proposing the inhibition of glucose transport by MLE. Next, dried mulberry leaf powder (MLP) was administered for 8 weeks by inclusion in the diet. By MLP administration, fasting blood glucose was significantly reduced at weeks 4 and 5 (P < 0.05), but then returned to values that were similar to those of the control at the end of experimental period in GK rats. Insulin, HOMA-IR, C-reactive protein, and triglycerides tended to be decreased by MLP treatment in GK rats. All other biochemical parameters were not changed by MLP administration in GK rats. Collectively, these findings support that MLE has significant postprandial hypoglycemic effect in both non-obese diabetic and healthy animals, which may be beneficial as food supplement to manage postprandial blood glucose. Inhibitions of glucose transport as well as alpha-glucosidase in the small intestine were suggested as possible mechanisms related with the postprandial hypoglycemic effect of MLE.

Keywords: Aqueous mulberry leaf extract; Goto-Kakizaki rats; postprandial hypoglycemic effect.

Figures

Fig. 1

Effects of MLE on postprandial blood glucose responses in GK rats (A) and their counterpart Wistar (B) rats (n=5 each group). The animals received orally administered maltose (2 g/kg body weight) with or without MLE (3.75 g/kg, 6 mg/kg as DNJ) after overnight fasting for 12h. Blood glucose levels were determined from tail blood samples at 0, 15, 30, 45, 60, 90, and 120 min and incremental blood glucose concentrations (ΔAUC0-2h) were integrated over a period of 2 h (Inset). Comparisons were done between MLE treated (■) and untreated control (□) rats: *P < 0.05, **P < 0.01.

Fig. 2

Effects of MLE on blood glucose increases 30 min after glucose-loading in GK rats and their counterpart Wistar rats (n=5 each group). The animals received orally administered glucose (2 g/kg) with or without MLE (3.75 g/kg, 6 mg/kg as DNJ) after overnight fasting for 12 h. Blood glucose levels were determined from tail blood samples at 0 and 30 min and the net increases were calculated. Comparisons were done between MLE treated (■) and untreated control (□) rats: **P < 0.01.

Fig. 3

Effects of MLP on fasting blood glucose concentrations in GK rats (A) and their counterpart Wistar (B) rats (n=10 each group). The animals were fed an AIG-93G diet with or without 10% MLP. The diets were adjusted to provide the same contents of dietary fiber and calories. Fasting blood glucose levels were determined from tail blood sample at fixed times. Comparisons were done between MLP treated and untreated control rats: P < 0.05.

Fig. 4

Effects of 10% MLP in the diet for 8 weeks on biochemical parameters of blood glucose, lipid, and inflammation control in GK rats and their counterpart Wistar rats (n=10 each group). A: fasting blood glucose (FBG), B: plasma insulin, C: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), D: Glycated hemoglobin (HbA1C), E: Advanced Glycation End Products (AGEs), F: C-Reactive Protein (CRP), G: Free Fatty Acids (FFAs), H: Triglyceride (TG). Comparisons were done between MLP treated (■) and untreated control (□) rats: P < 0.05.