To study molecular mechanisms by which KRG ameliorates diabetes mellitus, we investigated whether the supplementation with the aqueous extract of KRG as a dietary admixture (1 % , w/w) regulates the expressions of signaling molecules that are associated with insulin action, insulin secretion and pancreatic ¦Â-cell mass in spontaneously diabetic Goto-Kakizaki (GK) rats.
An aqueous extract of KRG was supplemented for the estimated dosage to be 0.2 g/kg rat/day beginning at 5 weeks of age for 12 weeks in male GK rats. Plasma glucose levels were measured every 4 weeks. The expressions of signaling molecules that are associated with insulin action, insulin secretion and ¦Â-cell mass in tissues were determined by Western blotting.
The 12-week supplementation with KRG significantly (P<0.05) decreased blood glucose compared to control. It up-regulated the expression of glucose transporter (GLUT) 4 in adipose tissue, and down-regulated the expression of protein tyrosine phosphatases (PTP)-1B in adipose tissue and skeletal muscle. It also up-regulated the expression of insulin and down-regulated the expression of uncoupling protein (UCP) 2, Bax and poly (ADP-ribose) polymerase (PARP) in pancreas.
These results suggest that GLUT4, PTP-1B, insulin, UCP2, Bax and PARP may be the primary targets of KRG that result in increase in insulin action and in insulin secretion, and decrease in ¦Â-cell mass, and that cause the normalization in glucose homeostasis.