열량공급제한이 OLETF 쥐의 간 PGC-1α 와 IGF-1 발현에 미치는 영향

Abstract

ABSTRACT

Attenuation of peroxisome proliferator-activated receptor gamma coactivator 1(PGC-1) alpha and insulin-like growth factor(IGF-1) on the response to caloric restriction in liver of Otsuka Long-Evans Tokushima Fatty Rats

Shin Ji-Hye Advisor : Prof. Bae Hak-Yeon M.D. Ph.D Department of Medicine, Graduate School of Chosun University

Background : PPAR gamma-coactivator 1(PGC-1) is regulated by costimulating the expression of key enzymes of gluconeogenetic pathway. PGC-1 is negatively regulated by insulin like growth factor(IGF-1) dependent pathway. We investigated the response to caloric restriction(CR) on the PGC-1, glucose-6-phosphate(G6Pase) and IGF-1 in liver of diabetic rats.

Method : Diabetic Otsuka Long-Evans Tokushima Fatty(OLETF) rats(male, aged 24 weeks) and non-diabetic Long-Evans Tokushima Otsuka(LETO) rats(male, aged 24 weeks) were used in this study. Liver PPARs and PGC-1 mRNA, IGF-1, insulin-like growth factor binding protein(IGFBP)-1, G6Pase and blood glucose levels were investigated at 3 weeks after the beginning of 15% CR.

Result : The liver PGC-1 mRNA levels were increased to 21% in LETO rats by 15% CR but significant change was not observed in OLETF rats by 15% CR. The difference of PPARs mRNA levels in liver of OLETF and LETO rats were not observed by 15% CR. The liver G6Pase activity was increased to 20% in LETO rats but changes were not significant in diabetic OLETF rats by CR. In OLETF rats, plasma IGF-1 and IGFBP-1 levels were lower than LETO rats by 40% and 25%, respectively. The plasma IGF-1 level was increased to 20% in OLETF rats by 15% CR but change was not significant in LETO rats by 15% CR. The liver IGF-1 and IGFBP-1 levels were increased to 30% and 42% in OLETF rats by 15% CR but significant change was not observed in LETO rats by 15% CR.

Conclusion : These findings suggest that PGC-1 and IGF-1 control system altered in diabetic OLETF rat liver and decreased IGF-1 expression may have some role in the aberrantly activated gluconeogenesis in diabetes mellitus by PGC-1.

Key word : PGC-1, Caloric restriction, IGF-1, OLETF rats