Sharma Ashwani, Virmani Tarun, Sharma Anjali, Chhabra Vaishnavi, Kumar Girish, Pathak Kamla, Alhalmi Abdulsalam
School of Pharmaceutical Sciences, MVN University, Palwal, Haryana, 121105, India.
Freelancer, Pharmacovigilance Expert, Uttar Pradesh, India.
Diabetes Metab Syndr Obes. 2022 Jun 16;15:1845-1864. doi: 10.2147/DMSO.S369712. eCollection 2022.
Dipeptidyl-peptidase-4 (DPP-4) is an enzyme having various properties and physiological roles in lipid accumulation, resistance to anticancer agents, and immune stimulation. DPP-4 includes membrane-bound peptidases and is a kind of enzyme that cleaves alanine or proline-containing peptides such as incretins, chemokines, and appetite-suppressing hormones (neuropeptide) at their N-terminal dipeptides. DPP-4 plays a role in the final breakdown of peptides produced by other endo and exo-peptidases from nutritious proteins and their absorption in these tissues. DPP-4 enzyme activity has different modes of action on glucose metabolism, hunger regulation, gastrointestinal motility, immune system function, inflammation, and pain regulation. According to the literature survey, as DPP-4 levels increase in individuals with liver conditions, up-regulation of hepatic DPP-4 expression is likely to be the cause of glucose intolerance or insulin resistance. This review majorly focuses on the cleavage of alanine or proline-containing peptides such as incretins by the DPP-4 and its resulting conditions like glucose intolerance and cause of DPP-4 level elevation due to some liver conditions. Thus, we have discussed the various effects of DPP-4 on the liver diseases like hepatitis C, non-alcoholic fatty liver, hepatic regeneration and stem cell, hepatocellular carcinoma, and the impact of elevated DPP-4 levels in association with liver diseases as a cause of glucose intolerance and their treatment drug of choices. In addition, the effect of DPP-4 inhibitors on obesity and their negative aspects are also discussed in brief.
二肽基肽酶-4（DPP-4）是一种在脂质积累、抗癌药物抗性和免疫刺激方面具有多种特性和生理作用的酶。DPP-4包括膜结合肽酶，是一种在其N端二肽处切割含丙氨酸或脯氨酸的肽（如肠促胰岛素、趋化因子和食欲抑制激素（神经肽））的酶。DPP-4在由其他内切和外切肽酶从营养蛋白质产生的肽的最终分解及其在这些组织中的吸收中起作用。DPP-4酶活性在葡萄糖代谢、饥饿调节、胃肠蠕动、免疫系统功能、炎症和疼痛调节方面具有不同的作用模式。根据文献调查，随着肝病患者DPP-4水平的升高，肝脏DPP-4表达上调可能是葡萄糖不耐受或胰岛素抵抗的原因。本综述主要关注DPP-4对含丙氨酸或脯氨酸的肽（如肠促胰岛素）的切割及其导致的葡萄糖不耐受等情况，以及某些肝病导致DPP-4水平升高的原因。因此，我们讨论了DPP-4对丙型肝炎、非酒精性脂肪肝、肝脏再生与干细胞、肝细胞癌等肝脏疾病的各种影响，以及与肝脏疾病相关的DPP-4水平升高作为葡萄糖不耐受原因及其治疗药物选择的影响。此外，还简要讨论了DPP-4抑制剂对肥胖的影响及其负面影响。
