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

Abstract

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

Abbreviations

GIP, Glucose-dependent insulinotropic peptide; GLP, Glucagon-like peptide; VIP, Vasoactive intestinal peptide; PACAP-38, Pituitary adenylate cyclase-activating polypeptide-38; GRP, Gastrin-releasing peptide; NPY, Neuropeptide Y; RANTES, Regulated upon activation; CCL, Chemokine (C-C motif) ligand; CXCL, Chemokine (C-X-C motif) ligand; SDF-1, Stromal-derived factor-1; MDC, Macrophage-derived chemokine; MIg, Monokine induced by gamma interferon; IP-10, Protein 10 from interferon (γ)-induced cell line; GHRH, Growth hormone-releasing hormone; I-TAC, Interferon-inducible T-cell α chemoattractant; LHα, Leutinizing hormone α chain; IGF-1, Insulin-like growth factor-1; CGRP, Calcitonin-related peptide; hCGα, Human chorionic gonadotropin α subunit.

Disclosure

The authors declare no conflicts of interest in relation to this work.