孕期咖啡因暴露致子代大鼠高脂饮食下胰腺形态和糖代谢功能改变

Changes of pancreatic morphology and glucose metabolism in prenatal caffeine-exposed offspring rats fed by post-weaning high-fat diet

目的:研究孕期咖啡因暴露(PCE)子代高脂饮食(HFD)下胰腺形态和糖代谢功能变化。方法:孕鼠妊娠第11天给予咖啡因120 mg·kg^(-1)·d^(-1)至自然生产。出生后4周给予HFD至成年。于出生后第20周行口服糖耐量(OGTT)实验。24周处死后,观察胰腺形态,检测肝胰岛素受体(IR)、胰岛素受体底物2(IRS2)和葡萄糖转运体2(Glut2)的mRNA表达。结果:与对照组相比,PCE组子代出生1周体质量降低但体质量增长率均升高(P<0.05,P<0.01),第4～24周雄性体质量降低而雌性升高(P<0.05,P<0.01)。第20周PCE组雌性子代基础血糖水平升高而胰岛素水平降低,定量胰岛素敏感性检测指数(QUICKI)升高(P<0.01)。同时,绝对糖耐量减低而相对糖耐量增强。与对照组相比,第24周PCE组胰岛形态被破坏,出现大量脂肪空泡变性。雌性子代肝IR、IRS2和Glut2的mRNA表达升高(P<0.05,P<0.01)。结论:PCE成年子代HFD下呈现"高血糖、低血胰岛素"为主的糖尿病样反应且以雌性较为明显,其机制可能与胰岛形态和功能损伤所致的胰岛素分泌不足有关。

OBJECTIVE To study the prenatal caffeine exposed(PCE)induced changes of pancreatic morphology and glucose metabolism in offspring rats fed by high-fat diet(HFD).METHODS From GD11 to normal spontaneous delivery,pregnant rats were given caffeine 120 mg·kg-1·d-1.HFD was administered 4 weeks after birth into adulthood.Oral glucose tolerance(OGTT)test was performed on postnatal week(PW)20.On PW24,the offspring were sacrificed and pancreatic morphology was observed to detect the mRNA expression of hepatic insulin receptor(IR),insulin receptor substrate 2(IRS2),and glucose transporter 2(GLUT2).RESULTS Compared with the control group,he offspring of the PCE group had lower body mass but higher body mass growth rate at 1 week(P<0.05,P<0.01),and the male body mass was reduced while the female body mass was increased during PW4-PW24(P<0.05,P<0.01).On PW20,the basal blood glucose level was increased and insulin level was reduced in female offspring of PCE group,and the quantitative insulin sensitivity index(QUICKI)was increased(P<0.01).Meanwhile,the absolute glucose tolerance was decreased but the relative glucose tolerance was increased.Compared with the control group,the morphology of islets in the PCE group was disrupted and massive fat vacuolar degeneration was observed at week 24.The mRNA expression of hepatic IR,IRS2,and GLUT2 was elevated in female offspring(P<0.05,P<0.01).CONCLUSION Hyperglycemia and low blood insulin are the main type of diabetic reaction in adult offspring of PCE under HFD,which is more obvious in females.The mechanism may be related to insulin secretion deficiency caused by the damage of islet morphology and function.