Antioxidant and Anti-Inflammatory Properties of Incretin-Based Therapies—Implications for Acute and Chronic Disease

Glucagon-like peptide (GLP-1) is an incretin hormone released from L-cells in the intestine after food uptake. Circulating GLP-1 binds to its receptor, which is expressed on pancreatic beta-cells, but also on various other cell types such as cardiomyocytes, endothelial cells, and inflammatory cells. The GLP-1 receptor belongs to the family of G-protein-coupled receptors and largely contributes to glucose homeostasis. In beta-cells of the pancreas, activation of the GLP-1 receptor increases intracellular cAMP levels, which stimulates insulin release and reduces glucagon release from alpha-cells. Based on these physiological actions of GLP-1 in glycemic control, GLP-1 analogs such as liraglutide, semaglutide, and dulaglutide (synthetic peptides with an almost similar chemical structure but significantly increased biological half-life) represent a new therapeutic option treating Type 2 diabetes. Similarly, inhibitors of the exopeptidase dipeptidyl peptidase-4 (DPP-4, also known as CD26) comprise the new drug class of gliptins for the treatment of diabetes, as they prevent the proteolytic degradation of GLP-1 by DPP-4 and thereby increase the half-life and bioavailability of GLP-1. Both drug classes, GLP-1 analogs and gliptins, are meanwhile a successful mainstay in modern antidiabetic therapeutic management. Importantly, GLP-1 analogs and gliptins have potent anti-inflammatory and antioxidant as well as other pleiotropic beneficial effects (e.g., direct vasodilation) that may indicate their use also in other chronic inflammatory, metabolic, cardiovascular, and neurodegenerative diseases (e.g., atherosclerosis, thrombosis, sepsis, non-alcoholic steatohepatitis, Alzheimer’s disease). In this Special Issue, we invite the submission of manuscripts that cover the following topics, preferably through in vivo studies at the preclinical (animal) and clinical (human) level combining functional and mechanistic data:

• Improvement of the pathophysiology of the abovementioned chronic diseases in either animal models or patients by treatment with one of the mentioned drug classes—preferably phenotypic characterization with mechanistic insight into the mode of action of the drugs;
• Proof-of-concept studies showing that GLP-1 analogs and gliptins act as anti-inflammatory and antioxidant or by another mechanism via well-characterized pleiotropic effects; these studies should use well accepted markers of inflammation or oxidative stress (or another process) that are assessed by state-of-the-art techniques, preferably using at least two complementary methods;
• Cell culture studies will only be considered if they provide deep mechanistic insights and data from at least two different cell types; these studies should use superior techniques, not only ELISA and other descriptive biomarkers.

Dr. Sebastian Steven
Prof. Dr. Andreas Daiber
Guest Editors

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