Abstract
The present study was designed to determine the antihyperglycemic function of ginsenoside
Rh2 (GS-Rh2) by the regeneration of β-cells in mice that underwent 70% partial pancreatectomy
(PPx), and to explore the mechanisms of GS-Rh2-induced β-cell proliferation. Adult
C57BL/6J mice were subjected to PPx or a sham operation. Within 14 days post-PPx,
mice that underwent PPx received GS-Rh2 (1 mg/kg body weight) or saline injection.
GS-Rh2-treated mice exhibited an improved glycemia and glucose tolerance, an increased
serum insulin levels, and β-cell hyperplasia. Meanwhile, increased β-cell proliferation
percentages and decreased β-cell apoptosis percentages were also observed in GS-Rh2-treated
mice. Further studies on the Akt/Foxo1/PDX-1 signaling pathway revealed that GS-Rh2
probably induced β-cell proliferation via activation of Akt and PDX-1 and inactivation
of Foxo1. Studies on the abundance and activity of cell cycle proteins suggested that
GS-Rh2-induced β-cell proliferation may ultimately be achieved through the regulation
of cell cycle proteins. These findings demonstrate that GS-Rh2 administration could
inhibit the tendency of apoptosis, and reverse the impaired β-cell growth potential
by modulating Akt/Foxo1/PDX-1 signaling pathway and regulating cell cycle proteins.
Induction of islet β-cell proliferation by GS-Rh2 suggests its therapeutic potential
in the treatment of diabetes.
Key words
islet regeneration - partial pancreatectomy - ginsenoside Rh2 (GS-Rh2) - cyclin D-Cdk4
complex - Akt/Foxo1/PDX-1 signaling pathway