Intrauterine growth retardation leads to the development of type 2 diabetes in the rat
Intrauterine growth retardation leads to the development of type 2 diabetes in the rat
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DOI：
10.2337/diabetes.50.10.2279
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发表时间：
2001-10-01
期刊：
影响因子：
7.7
通讯作者：
Gertz, SJ
中科院分区：
文献类型：
--
作者：
Simmons, RA;Templeton, LJ;Gertz, SJ
宫内发育迟缓与以后患2型糖尿病有关。这种现象背后的机制尚不清楚。我们在大鼠中建立了子宫胎盘功能不全的模型，子宫胎盘功能不全是宫内发育迟缓的常见原因。孕鼠于妊娠第19天（足月22天）结扎双侧子宫动脉，假手术组孕鼠作为对照。宫内生长迟缓（IUGR）动物的出生体重显着低于对照组，直到7周龄，当IUGR大鼠赶上对照组。7 ~ 10周龄IUGR大鼠生长速度加快，超过对照组，26周龄IUGR大鼠肥胖（P < 0.05）。1周龄时血糖和血浆胰岛素水平无显著差异。然而，在7 - 10周龄之间，IUGR大鼠出现轻度空腹高血糖和高胰岛素血症（与对照组相比P < 0.05）。在26周龄时，IUGL动物具有显著升高的葡萄糖水平（与对照组相比P < 0.05）。IUGR动物在早期就出现葡萄糖不耐受和胰岛素抵抗。在IUGR大鼠生命早期，在高血糖发作之前，对葡萄糖的第一时相胰岛素分泌也受损。在1周龄和7周龄时，IUGR和对照组动物之间的β细胞质量、胰岛大小或胰腺重量没有显著差异。而15周龄IUGR大鼠的β细胞相对质量为对照组的50%，26周龄时β细胞相对质量小于对照组的1/3（P < 0.05）。本文提供的数据支持这一假设，即异常的宫内环境可以诱导出生后葡萄糖稳态的永久性变化，并导致成年后的2型糖尿病。
Intrauterine growth retardation has been linked to the development of type 2 diabetes in later life. The mechanisms underlying this phenomenon are unknown. We have developed a model of uteroplacental insufficiency, a common cause of intrauterine growth retardation, in the rat. Bilateral uterine artery ligation was performed on day 19 of gestation (term is 22 days) in the pregnant rat; sham-operated pregnant rats served as controls. Birth weights of intrauterine growth-retarded (IUGR) animals were significantly lower than those of controls until similar to7 weeks of age, when IUGR rats caught up to controls. Between 7 and 10 weeks of age, the growth or IUGR rats accelerated and surpassed that of controls, and by 26 weeks of age, IUGR rats were obese (P < 0.05 vs. controls). No significant differences were observed in blood glucose and plasma insulin levels at 1 week of age. However, between 7 and 10 weeks of age, IUGR rats developed mild fasting hyperglycemia and hyperinsulinemia (P < 0.05 vs. controls). At age 26 weeks, IUGL' animals had markedly elevated levels of glucose (P < 0.05 vs. controls). IUGR animals were glucose-intolerant and insulin-resistant at an early age. First-phase insulin secretion in response to glucose was also impaired early in life in IUGR rats, before the onset of hyperglycemia. There were no significant differences in beta -cell mass, islet size, or pancreatic weight between IUGR and control animals at I and 7 weeks of age. However, irk 15-week-old IUGR rats, the relative beta -cell mass was 50% that of controls, and by 26 weeks of age, beta -cell mass was less than one-third that of controls (P < 0.05). The data presented here support the hypothesis that an abnormal intrauterine milieu can induce permanent changes in glucose homeostasis after birth and lead to type 2 diabetes in adulthood.