膳食丙烯酰胺暴露对2型糖尿病大鼠血糖代谢及脏器功能的影响

Effect of Dietary Acrylamide Exposure on Blood Glucose Metabolism and Organ Functions of Type 2 Diabetic GK Rats

目的:探讨膳食丙烯酰胺暴露对2型糖尿病大鼠病程进展的影响。方法:对糖尿病模型GK大鼠给予低剂量丙烯酰胺(2 mg/(kg mb·d))8周后,研究其对大鼠空腹血糖、空腹糖耐量和胰岛素敏感性等血糖代谢相关指标的影响,同时测定血清生化指标、氧化和炎症因子水平,并对肝脏、肾脏、胰腺和腓肠肌进行苏木精-伊红染色,观察病理变化情况,分析丙烯酰胺暴露对GK大鼠脏器组织功能的影响。最后采用气相色谱-质谱联用仪对大鼠血清和尿液中的代谢物进行检测,筛选膳食丙烯酰胺暴露对GK大鼠造成影响的主要差异代谢物,分析其关联的代谢通路。结果:与对照组(灌胃去离子水)相比,膳食丙烯酰胺暴露进一步通过损伤GK大鼠胰腺、促进氧化炎症应激、影响胰岛β细胞功能和磷酸戊糖代谢通路等作用,导致糖尿病模型GK大鼠血糖代谢紊乱加重,具体表现为空腹血糖水平明显上升、空腹糖耐量受损和胰岛素敏感性降低。此外,膳食丙烯酰胺暴露的GK大鼠体内显著改变的差异代谢物有L-酪氨酸、肌醇、马尿酸、柠康酸、苯乙酰甘氨酸、N-乙酰基亮氨酸、喹啉酸、L-色氨酸以及5-羟甲基色胺等,与精氨酸和脯氨酸代谢、色氨酸代谢、磷酸肌醇代谢、苯丙氨酸、酪氨酸和色氨酸代谢等氨基酸代谢有关,这些受影响的代谢物和代谢通路被认为与肝脏功能和神经组织功能异常相关。结合血清生化和病理分析证实,膳食丙烯酰胺暴露对GK大鼠肝脏、腓肠肌及神经组织造成了不同程度的损伤。结论:膳食丙烯酰胺暴露对糖尿病模型GK大鼠的健康造成严重不良影响,加剧血糖代谢紊乱,影响脏器组织功能。

Objective:To investigate the effect of dietary acrylamide exposure on the progression of type 2 diabetes in GK rats.Methods:The effects of intragastric administration of acrylamide(2 mg/(kg mb·d)) for eight weeks on blood glucose metabolism indicators in GK rats including fasting blood glucose,fasting glucose tolerance and insulin sensitivity were evaluated.Meanwhile,the levels of serum biochemical indexes,oxidative stress and inflammatory factors were determined,and pathological changes of the liver,kidney,pancreas and gastrocnemius muscle were observed by hematoxylin-eosin(HE) staining to examine the effect of acrylamide exposure on organ functions of GK rats.In addition,serum and urine metabolites were detected by gas chromatography-mass spectrometry(GC-MS),the major differential metabolites between the acrylamide exposure and control(deionized water) groups were identified and related metabolic pathways were analyzed.Results:Compared with the control group,dietary acrylamide exposure further damaged the pancreas of GK rats,promoted oxidative stress and inflammatory factors,and affected islet β-cell function and the pentose phosphate metabolic pathway,aggravating blood glucose metabolism disorder,as manifested by a significant increase in fasting blood glucose levels(P 0.05),impaired fasting glucose tolerance and decreased insulin sensitivity.In addition,the differential metabolites identified included L-tyrosine,inositol,hippuric acid,citraconic acid,phenylacetylglycine,N-acetylleucine,quinolinic acid,L-tryptophan and 5-hydroxymethyltryptamine,which were associated with the metabolic pathways of amino acids such as arginine,proline,tryptophan,phosphoinositide,phenylalanine,tyrosine and tryptophan.These metabolites and metabolic pathways are thought to be associated with abnormal liver and neural tissue functions.Serum biochemical and pathological analysis confirmed that dietary acrylamide exposure could cause different degrees of damage to the liver,gastrocnemius muscle and nerve tissue of GK rats.Conclusion:Dietary acrylamide exposure has serious adverse effects on the health of diabetic GK rats,aggravating blood glucose metabolism disorder and affecting the function of organs and tissues.