Capsaicin Reduces Blood Glucose by Increasing Insulin Levels and Glycogen Content Better than Capsiate in Streptozotocin-Induced Diabetic Rats.

Chili peppers exhibit antiobesity, anticancer, antidiabetic, and pain- and itch-relieving effects on animals and humans; these effects are due to capsaicin, which is the main pungent and biologically active component of pepper. Capsiate, a nonpungent capsaicin analogue, is similar to capsaicin in terms of structure and biological activity. In this study, we investigated whether capsaicin and capsiate exhibit the same hypoglycemic effects on rats with type 1 diabetes (T1D). Experimental rats were categorized into four groups: control, model, capsaicin, and capsiate groups. The two treatment groups were treated orally with 6 mg/kg bw capsaicin and capsiate daily for 28 days. Treatment with capsaicin and capsiate increased body weight, increased glycogen content, and inhibited intestinal absorption of sugar in T1D rats. Particularly, insulin levels were increased from 14.9 ± 0.76 mIU/L (model group) to 22.4 ± 1.39 mIU/L (capsaicin group), but the capsiate group (16.7 ± 0.79 mIU/L) was increased by only 12.2%. Analysis of the related genes suggested that the transient receptor potential vanilloid 1 (TRPV1) receptor was activated by capsaicin. Liver X receptor and pancreatic duodenum homeobox 1 controlled the glycometabolism balance by regulating the expression levels of glucose kinase, glucose transport protein 2 (GLUT2), phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase, leading to reduced blood glucose levels in T1D rats. Meanwhile, the hypoglycemic effect was enhanced by the down-regulated expression of sodium glucose cotransporter 1, GLUT2, and GLUT5 in the intestine. The results showed that the spicy characteristics of capsaicin might be the root of its ability to decrease blood glucose.