Red Ginseng Administration Before Islet Isolation Attenuates Apoptosis and Improves Islet Function and Transplant Outcome in a Syngeneic Mouse Marginal Islet Mass Model.
BACKGROUND
Transplantation of isolated islets is a promising treatment for diabetes. Red ginseng (RG) is steamed ginseng and has been reported to enhance insulin secretion-stimulating and anti-apoptotic activities in pancreatic β-cells. In this study, we examined the hypothesis that pre-operative RG treatment enhances islet cell function and anti-apoptosis and investigated whether RG improves islet engraftment by transplant of a marginal mass of syngeneic islets pretreated with RG in diabetic mice.


METHODS
Balb/c mice were randomly divided into 2 groups, and 1 group was administered RG (400 mg/kg/day orally) for 7 days before islet isolation. In vitro islet viability and function were assessed. After cytokine treatment, cell viability, function, and apoptosis of islet cells were analyzed. Furthermore, we studied the effects of RG in a syngeneic islet graft model. A marginal mass of syngeneic mouse islets was transplanted into diabetic hosts.


RESULTS
Islet pretreatment with RG showed 1.4-fold higher glucose-induced insulin secretion than did control islets. RG pretreatment upregulated B-cell lymphoma 2 (Bcl-2) expression and downregulated Bcl-associated X protein (BAX), caspase-3, and inducible nitric oxide synthase (iNOS) expression. Glucose-induced insulin release, NO, and apoptosis were significantly improved in RG-pretreated islets compared with cytokine-treated islets. RG-pretreated mice exhibited improved marginal mass islet graft survival compared with controls.


CONCLUSIONS
These results suggest that pre-operative RG administration enhanced islet function before transplantation and attenuated cytokine-induced damage associated with apoptosis. These studies indicate that inhibition of apoptosis by RG significantly improved islet cell and graft function after isolation and transplantation, respectively.
Department of Anesthesia and Pain Medicine, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
J S
JS
Kim
Department of Surgery, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea. Electronic address: jhj@gnah.co.kr.
H J
HJ
Jang
Department of Anesthesia and Pain Medicine, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
S S
SS
Kim
Department of Surgery, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
M Y
MY
Oh
Department of Surgery, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
H J
HJ
Kim
Department of Surgery, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
S Y
SY
Lee
Department of Pathology, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
D W
DW
Eom
Natural Medicine Center, Korea Institute of Science and Technology (KIST), Gangneung, Seoul, South Korea.
J Y
JY
Ham
Asan Medical Center, Seoul, South Korea.
D J
DJ
Han
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000601:surgery; D004334:Drug Administration Schedule; D006085:Graft Survival / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D005894:Panax; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011300:Preoperative Care / Q000379:methods*; D011897:Random Allocation
D015415:Biomarkers; D010936:Plant Extracts