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Diabetes: What Roles Does DPP4 Inhibition Have?
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Diabetes: What Roles Does DPP4 Inhibition Have?

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 9115

Special Issue Editor

Prof. Dr. Mark Gorrell

E-Mail Website
Guest Editor
Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
Interests: DPP4; peptidases; cell biology; diabetes; Covid_19; liver fibrosis; fatty liver; liver cancer

Special Issue Information

Dear Colleagues,

DPP4 inhibition was the first new medicine for type 2 diabetes mellitus (T2DM) in the 21st century, having its origins in the 1990s. The path to a therapy began with the discovery that DPP4 is the most important protease that inactivates GLP1. Until then, the focus of DPP4 research was in its immunological roles. The discoveries that DPP4 is the major receptor for infection of human cells by the MERS virus, and severe MERS is associated with T2DM, linked DPP4 also with virology. Naturally, potential roles for DPP4 in Covid_19 are being studied. Research on DPP4 inhibition has investigated potential benefits for diabetes complications such as cardiovascular disease, fatty liver and inflammation as well as associations between DPP4 and obesity and turning towards immunology and cancer biology.

DPP4 is a multifunctional protein having numerous biological roles because it cuts and inactivates many substrates. Much of the challenge has been to identify the size, circumstances and impact of DPP4 mediated effects.

This special issue will contain all these aspects of DPP4 in biology and medicine, according to the areas of interest to the invited authors.

Prof. Dr. Mark Gorrell
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • DPP4
  • diabetes
  • diabetes complications
  • pathogenesis
  • therapy
  • cancer biology
  • immunology

Published Papers (2 papers)

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Research

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14 pages, 5533 KiB  
Article
Sitagliptin Is More Effective Than Gliclazide in Preventing  Pro-Fibrotic and Pro-Inflammatory Changes in a Rodent Model of Diet-Induced Non-Alcoholic Fatty Liver Disease
by Jing Ren, Xiaoyu Wang, Christine Yee, Mark D. Gorrell, Susan V. McLennan and Stephen M. Twigg
Molecules 2022, 27(3), 727; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030727 - 22 Jan 2022
Cited by 7 | Viewed by 3211
Abstract
A diet-induced non-alcoholic fatty liver disease (NAFLD) model causing obesity in rodents was used to examine whether sitagliptin and gliclazide therapies have similar protective effects on pathological liver change. Methods: Male mice were fed a high-fat diet (HFD) or standard chow (Chow) ad [...] Read more.
A diet-induced non-alcoholic fatty liver disease (NAFLD) model causing obesity in rodents was used to examine whether sitagliptin and gliclazide therapies have similar protective effects on pathological liver change. Methods: Male mice were fed a high-fat diet (HFD) or standard chow (Chow) ad libitum for 25 weeks and randomly allocated to oral sitagliptin or gliclazide treatment for the final 10 weeks. Fasting blood glucose and circulating insulin were measured. Inflammatory and fibrotic liver markers were assessed by qPCR. The second messenger ERK and autophagy markers were examined by Western immunoblot. F4/80, collagens and CCN2 were assessed by immunohistochemistry (IHC). Results: At termination, HFD mice were obese, hyperinsulinemic and insulin-resistant but non-diabetic. The DPP4 inhibitor sitagliptin prevented intrahepatic induction of pro-fibrotic markers collagen-IV, collagen-VI, CCN2 and TGF-β1 and pro-inflammatory markers TNF-α and IL-1β more effectively than sulfonylurea gliclazide. By IHC, liver collagen-VI and CCN2 induction by HFD were inhibited only by sitagliptin. Sitagliptin had a greater ability than gliclazide to normalise ERK-protein liver dysregulation. Conclusion: These data indicate that sitagliptin, compared with gliclazide, exhibits greater inhibition of pro-fibrotic and pro-inflammatory changes in an HFD-induced NAFLD model. Sitagliptin therapy, even in the absence of diabetes, may have specific benefits in diet-induced NAFLD. Full article
(This article belongs to the Special Issue Diabetes: What Roles Does DPP4 Inhibition Have?)
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Review

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17 pages, 628 KiB  
Review
Role of Dipeptidyl Peptidase 4 Inhibitors in Antidiabetic Treatment
by Ruili Yin, Yongsong Xu, Xin Wang, Longyan Yang and Dong Zhao
Molecules 2022, 27(10), 3055; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27103055 - 10 May 2022
Cited by 22 | Viewed by 5397
Abstract
In recent years, important changes have occurred in the field of diabetes treatment. The focus of the treatment of diabetic patients has shifted from the control of blood glucose itself to the overall management of risk factors, while adjusting blood glucose goals according [...] Read more.
In recent years, important changes have occurred in the field of diabetes treatment. The focus of the treatment of diabetic patients has shifted from the control of blood glucose itself to the overall management of risk factors, while adjusting blood glucose goals according to individualization. In addition, regulators need to approve new antidiabetic drugs which have been tested for cardiovascular safety. Thus, the newest class of drugs has been shown to reduce major adverse cardiovascular events, including sodium-glucose transporter 2 (SGLT2) and some glucagon like peptide 1 receptor (GLP1) analog. As such, they have a prominent place in the hyperglycemia treatment algorithms. In recent years, the role of DPP4 inhibitors (DPP4i) has been modified. DPP4i have a favorable safety profile and anti-inflammatory profile, do not cause hypoglycemia or weight gain, and do not require dose escalation. In addition, it can also be applied to some types of chronic kidney disease patients and elderly patients with diabetes. Overall, DPP4i, as a class of safe oral hypoglycemic agents, have a role in the management of diabetic patients, and there is extensive experience in their use. Full article
(This article belongs to the Special Issue Diabetes: What Roles Does DPP4 Inhibition Have?)
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