Antihyperglycemic effect of ginsenoside Rh2 by inducing islet β-cell regeneration in mice.
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.
School of Life Science, Sichuan University, Chengdu, Sichuan, China.
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Y
Wang
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H
Wang
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Y
Liu
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C
Li
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P
Qi
J
J
Bao
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D056741:Cyclin D / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006965:Hyperplasia; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012038:Regeneration / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D056741:Cyclin D; D036145:Ginsenosides; D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; C055305:ginsenoside Rh2; D005947:Glucose