关键词: 丙烯酰胺；膳食暴露；2型糖尿病；代谢组学

Abstract: 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.

Key words: acrylamide; dietary exposure; type 2 diabetes; metabolomics