13th Congress of the Asian Society of Transplantation: General transplantation issue
Experimental transplantation
Ginsenoside Rg3 Enhances Islet Cell Function and Attenuates Apoptosis in Mouse Islets

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Abstract

Background

The transplantation of isolated islets is thought to be an attractive approach for curative treatment of diabetes mellitus. Panax ginseng has been used in oriental countries for its pharmacologic effects, such as antidiabetic and antiinflammatory activities. 20(S)-ginsenoside Rg3 (Rg3), an active ingredient of ginseng saponins, has been reported to enhance insulin secretion–stimulating and antiapoptotic activities in pancreatic beta cells. We performed this study to examine the hypothesis that preoperative Rg3 administration can enhance islet cell function and antiapoptosis before islet transplantation.

Methods

Balb/c mice were randomly divided into 2 groups according to the administration of Rg3 after islet isolation. Mouse islets were cultured in medium supplemented with or without Rg3. In vitro, islet viability and function were assessed. After treatment of islets with a cytokine cocktail (tumor necrosis factor α, interferon-γ, and interleukin-1β), cell viability, function, and apoptosis were assessed.

Results

Cell viability was similar between the 2 groups. Islets cultured in medium supplemented with Rg3 showed 2.3-fold higher glucose-induced insulin secretion than islets cultured in medium without Rg3. After treatment with a cytokine cocktail, glucose-induced insulin release, total insulin content of islets, and apoptosis were significantly improved in Rg3-treated islets compared with cytokine-treated islets. Cytokine-treated islets produced significantly higher levels of nitric oxide (NO) than islets treated with Rg3.

Conclusions

These results suggest that preoperative Rg3 administration enhanced islet function before islet transplantation and attenuated both cytokine-induced damage associated with NO production and apoptosis. Rg3 administration might be a prospective management to enhanced islet function and ameliorate early inflammation after transplantation.

Section snippets

Animals

Female Balb/c mice (12 weeks of age) were purchased from Jeung-Do Bio Plant Co (Seoul, Korea). Our study was reviewed and approved by the Animal Care and Use Committee of Korea Institute of Science and Technology (Gangneung, Korea).

20(S)-Ginsenoside Rg3 (Rg3)

Rg3 was purchased from Ambo Institute (South Korea), and dissolved in 0.1% dimethyl sulfoxide (DMSO). The chemical structure of Rg3 is shown in Fig 1.

Mouse Islet Isolation

Islets were isolated from Balb/c mice pancreas by a collagenase digestion procedure. After isolation, islets were

Results

Islet cell viability was assessed by diacetate–propidium iodide staining at 24, 48, and 72 hours after the isolation procedure. Viability values for the Rg3 groups were similar to those of the control groups at 24, 48, and 72 hours and showed no statistical difference between the 2 groups (Fig 2A). Rg3 suppressed the cleavage of PARP. PARP (116 kDa) is cleaved to produce an 89-kDa fragment during apoptosis. PARP cleavage, as evidenced by the accumulation of the 89-kDa species, was observed when

Discussion

This study indicates that mouse islet function (glucose-stimulated insulin secretion) can be increased by simple Rg3 culturing methods after the isolation procedure. In addition, we observed lower apoptotic levels in islets isolated from Rg3-cultured groups, indicating less inflammatory damage.

Islet transplantation is a promising treatment of diabetes mellitus [1]. However, it faces several challenges, including the loss of islet cell viability and function during the peritransplantation

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Funding: Gangneung Asan Hospital Biomedical Research Center Promotion Fund.

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