Dipartimento di Scienze della Vita e dell'Ambiente, Università degli Studi di Cagliari, Via Ospedale 42, 09124, Cagliari, Italy.
Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale 72-09124, Cagliari, Italy.
J Physiol Biochem. 2017 Nov;73(4):575-582. doi: 10.1007/s13105-017-0588-7. Epub 2017 Sep 11.
This study was achieved with the aim to find metabolic changes between Fischer rats with different dipeptidyl peptidase-type 4 (DPPIV) expression. The DPPIV is an enzyme expressed in several tissues and is critically involved in the regulation of meal-related insulin secretion in healthy individuals. The metabolic consequences of chronic DPPIV inhibition were analyzed in a surrogate animal model of genetic enzyme deficiency. Hyphenated gas chromatography-mass spectrometry (GC-MS) and multivariate data analysis techniques were used to study the metabolic aqueous fraction profile of 18 plasma and liver samples in two syngeneic rat strains differing in DPPIV activity (DPPIV vs. DPPIV). The hyperglycemic response following oral glucose administration was attenuated in DPPIV rats, as expected. Statistical significant differences between the two strains were observed among the low molecular weight polar metabolites analyzed from plasma and liver.These included a decrease in malic acid and glutamine and an increase in pyroglutamic acid, serine, and alanine in plasma of DPPIV rats. In addition, palmitic acid, L-proline, and ribitol were decreased in the liver of DPPIV strain. Such alterations were compatible with a normal phenotype. These results suggest that long-term exposure to DPPIV inhibitors looks compatible with an overall balanced metabolism.
本研究旨在寻找不同二肽基肽酶-4 (DPPIV) 表达水平的 Fischer 大鼠之间的代谢变化。DPPIV 是一种在多种组织中表达的酶，在健康个体的进餐相关胰岛素分泌调节中起着关键作用。本研究在遗传酶缺乏的替代动物模型中分析了慢性 DPPIV 抑制的代谢后果。使用气相色谱-质谱联用 (GC-MS) 和多变量数据分析技术研究了两种同基因大鼠（DPPIV 与 DPPIV）在 18 个血浆和肝脏样本的代谢水相谱。正如预期的那样，口服葡萄糖后，DPPIV 大鼠的高血糖反应减弱。在分析来自血浆和肝脏的低分子量极性代谢物时，两个品系之间观察到统计学上的显著差异。这些差异包括 DPPIV 大鼠血浆中苹果酸和谷氨酰胺减少，焦谷氨酸、丝氨酸和丙氨酸增加。此外，DPPIV 品系的肝脏中棕榈酸、L-脯氨酸和核糖醇减少。这些变化与正常表型相符。这些结果表明，长期暴露于 DPPIV 抑制剂与整体平衡的代谢相容。
