Liu Xiao-mei, Kong Jing, Song Wei-wei, Lu Yan
Central Laboratory, Shengjing Hospital, China Medical University, Shenyang 110004, China.
Chin Med Sci J. 2009 Dec;24(4):208-12. doi: 10.1016/s1001-9294(10)60003-x.
To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.
Male intrauterine growth restriction (IUGR) offspring induced by maternal protein-malnutrition and normal controls were studied. The body weights of offspring rats were weighted from birth to 12 weeks of age. Fasting plasma glucose and insulin levels were determined by glucose oxidase method and enzyme-linked immunosorbent assay (ELISA) respectively at 1 week, 8 weeks, and 12 weeks. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase) mRNA and protein levels in liver were measured by real time RT-PCR and Western blot in newborn rats (Week 1) and adult rats (Week 12).
Birth weights of IUGR rats were significantly lower than those of controls until 4 weeks later, when IUGR rats caught up to controls. Between 8 and 12 weeks, the growth of IUGR rats surpassed that of controls. No significant differences were observed in blood glucose and insulin levels at newborn rats between the two groups. However, by the end of 8 weeks IUGR rats developed hyperinsulinemia and high insulin resistance index. At the age of 12 weeks, IUGR rats had mild fasting hyperglycemia. In addition, hepatic PGC-1 alpha mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase at Week 1 and Week 12 in IUGR rats were all significantly higher than those of controls (P<0.05).
As a result of intrauterine malnutrition, the expression of gluconeogenic genes is exaggerated in offspring. This change stays through adulthood and may contribute to the pathogenesis of type 2 diabetes.
通过测定血糖及肝脏中糖异生酶的表达，探讨宫内生长受限成年大鼠2型糖尿病的分子机制。
研究母体蛋白质营养不良诱导的雄性宫内生长受限（IUGR）子代及正常对照。测定子代大鼠从出生至12周龄的体重。分别在1周、8周和12周时，采用葡萄糖氧化酶法和酶联免疫吸附测定（ELISA）法测定空腹血糖和胰岛素水平。通过实时逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法测定新生大鼠（第1周）和成年大鼠（第12周）肝脏中过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）、磷酸烯醇式丙酮酸羧激酶（PEPCK）和葡萄糖-6-磷酸酶（G6Pase）的mRNA和蛋白水平。
IUGR大鼠出生体重显著低于对照组，直到4周后IUGR大鼠体重赶上对照组。在8至12周期间，IUGR大鼠的生长超过对照组。两组新生大鼠的血糖和胰岛素水平无显著差异。然而，到8周龄时，IUGR大鼠出现高胰岛素血症和高胰岛素抵抗指数。在12周龄时，IUGR大鼠出现轻度空腹高血糖。此外，IUGR大鼠第1周和第12周肝脏中PGC-1α的mRNA和蛋白水平以及PEPCK和G6Pase的肝脏mRNA水平均显著高于对照组（P<0.05）。
由于宫内营养不良，子代中糖异生基因的表达过度。这种变化持续至成年期，可能促成2型糖尿病的发病机制。
