父代糖尿病对子代糖代谢的长期影响

Long-term Consequences of Paternal Diabetes on Glucose Regulation in the Offspring

探讨父代糖尿病对子代老年期糖代谢的潜在影响。健康雄性SD大鼠经腹腔注射链脲佐菌素(35 mg/kg)建立雄性大鼠糖尿病模型,并与健康SD雌鼠交配所得子代为处理组(STZ-O组);健康雄鼠与健康雌鼠交配所得子代为正常对照组(CON-O组)。两组动物出生后记录出生体重,标准饲料喂养至18月龄,测定随机血糖含量、血清胰岛素含量;进行葡萄糖耐量试验(glucose tolerance test,GTT)、胰岛素耐量试验(insulin tolerance test,ITT)检测胰岛素抵抗情况;丙酮酸耐量试验(pyruvic acid tolerance test,PTT)检测肝脏糖异生情况;经糖原染色观察肝脏糖原沉积情况;以Real-time PCR检测肝脏组织糖异生途径关键酶磷酸烯醇式丙酮酸羧激酶(PEPCK)、葡萄糖-6-磷酸酶(G-6-P)、果糖-1,6-磷酸酶(FBP)mRNA表达水平。结果表明:父代糖尿病可导致子代在老年期出现胰岛素抵抗,同时伴有肝脏糖异生作用增强。其具体作用机制仍有待进一步研究。

This study was designed to investigate the long-term consequences of paternal diabeties on the regulation of hepatic gluconeogenesis in the offspring. Diabetic male rat model was established by intraperitoneal injection of streptozotocin （35 mg/kg）, the offspring from diabetic male rats bred by female rats was STZ-O group, others from the healthy male rats mated with female rats was CON-O group. The birth weights of the offspring were recorded after delivery, ELISA was con- ducted to detect the serum insulin level, and glucose tolerance tests （GTr） and insulin tolerance tests （ITT） were measured to evaluate the condition of insulin resistance; pyruvic acid tolerance test （PTT） and real-time PCR were performed to assess the liver gluconeogenesis; periodic acid-schiff stain （PAS） tests was used to assess the liver glycogen deposition. The birth weights of STZ-O group were significantly decreased compared with CON-O group （6.63±0.46 VS 5.72±0.31 ,P = 0. 0013）. There was no difference of random blood glucose level between the two groups, whereas a significant difference was observed in serum insulin level （49.47 μIU/mL ± 15.63 μIU/mL in STZ-O group and 18.55 μIU/mL ±2.59 μIU/mL in CON-O group, P = 0.011 ）. There were also significant differences of GTF, 1TY, PTF and PAS staining results between the two groups. The expression of two key enzymes involving in hepatic gluconeogenesis, PEPCK and G-6-P, were up-regu- lated in the STZ-O group. All these results suggested that paternal diabetes would cause long-term consequences including insulin resistance and abnormal activation of hepatic gluconeogenesis on the offspring.