Potential Effect of DPP-4 Inhibitors Towards Hepatic Diseases and Associated Glucose Intolerance - PubMed (original) (raw)

Review

. 2022 Jun 16:15:1845-1864.

doi: 10.2147/DMSO.S369712. eCollection 2022.

Affiliations

Review

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

Ashwani Sharma et al. Diabetes Metab Syndr Obes. 2022.

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; DPP-4 inhibitors; glucose intolerance; incretins; insulin; liver diseases; sitagliptin.

© 2022 Sharma et al.

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Conflict of interest statement

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

Figures

Figure 1

Figure 1

Graphical representation of the concentration and activity of DPP-4 in different organs/tissues/cells.

Figure 2

Figure 2

Molecular structure of DPP-4.

Figure 3

Figure 3

Physiological properties of DPP-4 in various regions.

Figure 4

Figure 4

Role of Incretins and DPP-4 in glucose regulation.

Figure 5

Figure 5

Schematic representation of HCV infected hepatocytes releases IP-10 responsible for an immune response towards HCV infection but DPP-4 level elevated due to CD8+ cells attacked by HCV. Increased DPP-4 converted the IP-10 into an inactive form which suppresses the immune response and on the other hand DPP-4 results in glucose intolerance by degrading incretins. Interferon and DPP-4 inhibitors are found to be significant in both HCV resulting conditions.

Figure 6

Figure 6

Non-alcoholic fatty liver disease results in an increased level of DPP-4 expression leads to hepatic insulin sensitivity and liver steatosis but sitagliptin and omarigliptin improve the conditions.

Figure 7

Figure 7

Liver diseases cause an increase in DPP-4, which causes glucose intolerance and DPP-4 inhibitors lead to relief in glucose intolerance as well as in liver conditions.

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