CAJ | 학술논문

目的探讨exendin-4(exenatide)对高脂诱导胰岛素抵抗(IR)大鼠胰岛素敏感性(IS)改善的机制及对脂肪细胞因子的影响.方法健康雄性SD大鼠随机分为正常饮食组(NC)、高脂组(HF)和高脂+Exenatide组(HE).HE组给予exenatide(2μg/kg,日二次)腹腔注射6周,用静脉胰岛素耐量试验评价各组IS变化,观察各组肌肉和脂肪组织胰岛素信号传导、脂肪细胞因子表达和血浆浓度变化.结果 6周后,HE组Lee's指数、空腹血浆FFA、TG、TC均较NC组降低(P均＜0.01),IR明显改善;胰岛素刺激后HE组肌肉和脂肪组织IRS-1酪氨酸磷酸化升高(P＜0.05);HF和HE组血浆内脏脂肪素(visfatin)水平明显降低(P＜0.05,P＜0.01),但HE组脂联素(APN)血浆水平和脂肪组织mRNA表达明显高于HF和NC组(P均＜0.01).结论 Exenatide明显改善了高脂大鼠IR,其胰岛素增敏机制可能与增强IRS-1酪氨酸磷酸化以及对APN、visfatin等脂肪细胞因子的影响有关.
목적 탐토exendin-4(exenatide)대고지유도이도소저항(IR)대서이도소민감성(IS)개선적궤제급대지방세포인자적영향.방법 건강웅성SD대서수궤분위정상음식조(NC)、고지조(HF)화고지+Exenatide조(HE).HE조급여exenatide(2μg/kg,일이차)복강주사6주,용정맥이도소내량시험평개각조IS변화,관찰각조기육화지방조직이도소신호전도、지방세포인자표체화혈장농도변화.결과 6주후,HE조Lee's지수、공복혈장FFA、TG、TC균교NC조강저(P균＜0.01),IR명현개선;이도소자격후HE조기육화지방조직IRS-1락안산린산화승고(P＜0.05);HF화HE조혈장내장지방소(visfatin)수평명현강저(P＜0.05,P＜0.01),단HE조지련소(APN)혈장수평화지방조직mRNA표체명현고우HF화NC조(P균＜0.01).결론 Exenatide명현개선료고지대서IR,기이도소증민궤제가능여증강IRS-1락안산린산화이급대APN、visfatin등지방세포인자적영향유관.
Objective To investigate the effects of exendin-4 (exenatide) on insulin sensitivity and adipocytokine in high-fat-fed rats. Methods Rats were divided randomly into normal-chow group (NC), high-fat group (HF) and high-fat+exendin treated group (HE). HE rats were given exenatide (2 μg/kg) twice daily for 6 wk. The insulin sensitivity was evaluated by intravenous insulin tolerance test (IVITT). Insulin-stimulated changes in insulin signal transduction, visfatin and adiponectin mRNA expressions as well as their plasma levels were also observed in these rats. Results Plasma free fatty acids (FFA), triglyceride (TG), total cholesterol (TC) levels were significantly reduced after exenatide treatment (in HE rats all P<0.01). And IVITT parameters were also improved in these rats. Insulin-stimulated IRS-1 tyrosine phosphorylation was slightly increased in exenatide-treated rats as compared with HF rats (P<0.05). In addition,plasma visfatin level was significantly reduced in HF and HE groups as compared with controls (P<0.05 and P<0.01). The adiponectin mRNA expression in adipose tissues and circulating adiponectin level were significantly elevated in exenatide-treated rats as compared with untreated rats and controls (P<0.01). Conclusions Chronic exenatide treatment improves insulin resistance in high-fat-fed rats, and the changes of IRS-1 tyrosine phosphorylation and adiponectin may be related to the role of exenatide in elevating insulin sensitivity