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Compound K의 인슐린분비 및 탄수화물 대사에 미치는 영향

Effects of Compound K on Insulin Secretion and Carbohydrate Metabolism

  • 최윤숙 (경희대학교 약학대학 약물학 임상약학 교실) ;
  • 한기철 (경희대학교 약학대학 약물학 임상약학 교실) ;
  • 한은정 (경희대학교 약학대학 약물학 임상약학 교실) ;
  • 박금주 (경희대학교 약학대학 약물학 임상약학 교실) ;
  • 성종환 ((주)일화 중앙연구소) ;
  • 정성현 (경희대학교 약학대학 약물학 임상약학 교실)
  • Choi, Yun-Suk (Pharmacology and Clinical Pharmacy Lab, College of Pharmacy, Kyung Hee University) ;
  • Han, Gi-Cheol (Pharmacology and Clinical Pharmacy Lab, College of Pharmacy, Kyung Hee University) ;
  • Han, Eun-Jung (Pharmacology and Clinical Pharmacy Lab, College of Pharmacy, Kyung Hee University) ;
  • Park, Kum-Ju (Pharmacology and Clinical Pharmacy Lab, College of Pharmacy, Kyung Hee University) ;
  • Sung, Jong-Hwan (ILHWA Co. LTD. Central Research Center) ;
  • Chung, Sung-Hyun (Pharmacology and Clinical Pharmacy Lab, College of Pharmacy, Kyung Hee University)
  • 발행 : 2007.06.30

초록

진세노사이드의 인슐린 분비 활성을 비교해 본 결과 PPD 계열 진세노사이드가 인슐린의 분비를 촉진하는 경향을 보였으며, 그 중에서도 CK의 인슐린 분비 촉진 효과가 가장 뛰어났다. CK는 RIN-m5F cell line과 일차 배양한 췌장 소도 세포에서 용량 의존적으로 인슐린의 분비를 촉진하였고 이러한 CK의 인슐린 분비 촉진 기전은 ATP-sensitive $K^+$ 채널의 봉쇄에 의한 것임을 확인하였다. H4IIE cell line에서 간 세포내 당신생과 관련된 효소의 발현을 측정한 결과 CK는 dexamethasone/cAMP에 의한 PEPCK 와 G6Pase의 발현을 억제하였다. 이로 미루어 볼 때, CK는 간에서 당의 신생을 억제하여 공복 시 혈당을 감소시킬 수 있음을 시사하였다. 또한 3T3-L1 cell line에서 TG의 함량과 $PPAR-{\gamma}$ 유전자의 발현에 미치는 영향을 살펴본 결과 CK는 $PPAR-{\gamma}$의 발현을 억제하여 결과 지방세포의 분화를 억제하였다. 결론적으로 CK는 췌장에서 ATP-sensitive $K^+$ channel을 봉쇄함으로 인슐린 분비를 촉진시키고 또한 간세포에서 당 신생을 억제함으로 식후 및 공복 시 혈당을 감소시킬 것으로 기대된다.

Compound K (CK) is a final metabolite of panaxadiol ginsenosides. Although panax ginseng is known to have anti-diabetic activity, the active ingredient is not yet fully identified. Therefore, it would be interesting to know whether and how CK has an anti-diabetic activity. First, insulin secretion-stimulating activity of CK was examined using RIN-m5F cell line and primary cultured islets. CK enhanced the insulin secretion in a concentration dependent manner. This effect, however, was almost completely abolished in the presence of diazoxide, $K^+$ channel opener, indicating that the insulin secretion-stimulating activity of CK is presumably due to blockade of ATP sensitive $K^+$ channel. In addition, effects of CK on gene expressions of hepatic enzymes (phosphoenolpyruvate carboxykinase[PEPCK], glucose-6-phos-phatase[G6Pase]) and on adipocyte differentiation in H4IIE and 3T3-Ll cells, respectively, were examined. CK suppressed the induction of PEPCK and G6Pase mRNA expressions under the dexamethasone/cAMP stimulation condition. CK also reduced the $PPAR-{\gamma}$ mRNA expression and triglyceride accumulation in a dose dependent manner as compared to the control. The present study suggests that CK deserves to examine whether it shows an anti-diabetic activity in animal and human studies.

키워드

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  2. Isolation and identification of antiproliferative substances from ginseng fermented using Ganoderma lucidum mycelia vol.24, pp.2, 2015, https://doi.org/10.1007/s10068-015-0074-3