摘要
目的研究重组exendin-4对遗传性胰岛素抵抗糖尿病(OLETF)大鼠血糖和胰岛素分泌的影响以及与转录因子胰十二指肠同源盒因子(pdx-1)mRNA表达的关系。方法将雄性OLETF大鼠随机分成对照组及EX4 A、B、C组。对照组腹腔内注射生理盐水,EX4 A、B、C组分别腹腔内注射5、20、100μg/kg的exendin-4,每日1次。1周后行口服葡萄糖耐量试验及胰岛素释放试验。半定量RT-PCR检测胰腺pdx-1 mRNA表达。结果EX4注射组糖耐量改善,空腹、120 min血糖及高峰血糖均明显降低,胰岛素分泌明显增高,与对照组比较,差异有统计学意义(P<0.05)。B细胞功能指数(HOMA-B)EX4各组分别为98.18±29.14、73.74±22.19、135.86±58.62,与对照组(36.88±15.14)比较,差异有统计学意义(P<0.05)。而胰岛素抵抗指数(HOMA-IR)和胰岛素敏感指数(ISI)EX4 A、B组与对照组比较,差异无统计学意义。pdx-1 mRNA EX4各组分别是0.40±0.15、0.56±0.15和0.65±0.17,均明显高于对照组的0.24±0.13(P<0.05)。结论exendin-4能促进OLETF大鼠胰岛素分泌,改善大鼠糖耐量及B细胞功能,并上调pdx-1 mRNA的表达。
Objective To observe the effects of glucagon-like peptide-1 agonist exendin-4 on glucose and insulin level and the expression of transcription factor pdx-1 mRNA in diabetic animal model OLETF rat with genetic insulin resistance. Methods OLETF rats randomly divided into 4 groups： vehicle（control）, exendin-4 doses of 5 μg/kg（EX4 A）, 20 μg/kg（EX4 B）, 100 μ/kg（EX4C）. The exendin-4 was injected daily. Oral glucose tolerance test and insulin release test were performed after 7 days treatment. The pdx-1 mRNA expression was detected by RT-PCR. Results Glucose tolerance was improved in EX4 groups, fasting and postprandial glucose and peak glucose levels were significantly lower and insulin secret was statistically increased than in control group, P〈 0.05. The HOMA-B in EX4 groups（98.18±29.14, 73.74±22.19, 135.86±58.62 respectively） were also improved, much higher than that of 36.88 ±15.14 in control group, P〈0.05. While HOMA-IR were not significantly different in statistics among EX4 A ,EX4 B and control groups. The expressions ofpdx-1 mRNA in three EX4 groups were 0.40±0.15, 0.5620.15 and 0.65±0.1, notably elevated than 0. 24±0.13 in control group, P〈0.05. Conclusions The exendin-4 treatment enhances insulin secret, decreases glucose level, improves glucose tolerance and B-cell function, and up-regulates the pdx-1 mRNA expression in OLETF rat.
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2005年第12期914-917,共4页
Chinese Journal of Geriatrics
基金
上海市科技攻关项目(课题编号03411908)
