Ginseng might mediate its antidiabetic action through a variety of mechanisms, including actions on the insulin-secreting pancreatic β-cells and the target tissues that take up glucose. Korean white ginseng (KWG) and KRG, one of the heat-processed Korean ginsengs, have a long history as herbal remedies with antidiabetic effects. KWG has been reported to stimulate glucose-induced insulin release from pancreatic islets as a potentiator. The mode of the insulinotropic action of KRG was to act as an initiator for insulin release, not in a glucose-dependent manner. In general, the heat-processed KRG has been reported to have more potent pharmacological activities than nonprocessed KWG.
KRG significantly evoked a stimulation of insulin release in normal pancreatic rat islets and may act by inhibiting the KATP channel, thereby depolarizing the β-cells and stimulating Ca2+ influx. These findings suggest that P. ginseng has beneficial effects in the treatment of diabetes at least in part via the stimulation of insulin release. Antihyperglycemic and antiobese effects of P. ginseng berry extract have been observed; its major constituent is ginsenoside Re. Ginsenoside Rg3 enhanced glucose-stimulated insulin secretion and was further metabolized to ginsenoside Rh2 by human intestinal bacteria, which seems to be more effective. Intravenous injection of ginsenoside Rh2 into rats decreased plasma glucose and increased plasma insulin by activation of muscarinic M3 receptors in pancreatic β-cells via acetylcholine (ACH) release from cholinergic terminals. PPD ginsenoside potentiated an insulin secretion stimulated by a low concentration of glucose, and C-K, a final metabolite of PPD ginsenoside, showed the most potent insulin secretion in pancreatic β-cells through action on the KATP-channeldependent pathway.
These observations were confirmed in an oral glucose tolerance test in ICR mice. In db/db mice, multiple administration of C-K showed hypoglycemic effects and improved glucose tolerance with β-cell preservation. Both Rh2 and C-K appear to have some therapeutic value for the treatment of diabetes and might be useful candidates for the development of new antidiabetic drugs.