Potential Effect of DPP-4 Inhibitors Towards Hepatic Diseases and Associated Glucose Intolerance

Abstract

Ashwani Sharma,1 Tarun Virmani,1 Anjali Sharma,2 Vaishnavi Chhabra,1 Girish Kumar,1 Kamla Pathak,3 Abdulsalam Alhalmi4 1School of Pharmaceutical Sciences, MVN University, Palwal, Haryana, 121105, India; 2Freelancer, Pharmacovigilance Expert, Uttar Pradesh, India; 3Faculty of Pharmacy, Uttar Pradesh University of Medical Sciences, Uttar Pradesh, 206130, India; 4Department of Pharmaceutical Science, College of Pharmacy, Aden University, Aden, YemenCorrespondence: Abdulsalam Alhalmi, Department of Pharmaceutical Science, College of Pharmacy, Aden University, Aden, Yemen, Email [email protected]: 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.Keywords: DPP-4, insulin, incretins, glucose intolerance, liver diseases, sitagliptin, DPP-4 inhibitors

Keywords

• dpp-4
• insulin
• incretins
• glucose intolerance
• liver diseases
• sitagliptin
• dpp-4 inhibitors.