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Open Access Green as soon as Postprint is submitted to ZB.
Gut peptide agonism in the treatment of obesity and diabetes.
Compr. Physiol. 10, 99-124 (2019)
Obesity is a global healthcare challenge that gives rise to devastating diseases such as the metabolic syndrome, type-2 diabetes (T2D), and a variety of cardiovascular diseases. The escalating prevalence of obesity has led to an increased interest in pharmacological options to counteract excess weight gain. Gastrointestinal hormones such as glucagon, amylin, and glucagon-like peptide-1 (GLP-1) are well recognized for influencing food intake and satiety, but the therapeutic potential of these native peptides is overall limited by a short half-life and an often dose-dependent appearance of unwanted effects. Recent clinical success of chemically optimized GLP-1 mimetics with improved pharmacokinetics and sustained action has propelled pharmacological interest in using bioengineered gut hormones to treat obesity and diabetes. In this article, we summarize the basic biology and signaling mechanisms of selected gut peptides and discuss how they regulate systemic energy and glucose metabolism. Subsequently, we focus on the design and evaluation of unimolecular drugs that combine the beneficial effects of selected gut hormones into a single entity to optimize the beneficial impact on systems metabolism.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Glucagon-like Peptide-1; Gastric-inhibitory Polypeptide; Dependent Insulinotropic Polypeptide; Diet-induced Obese; Glp-1 Receptor Agonist; Pancreatic Beta-cells; Improves Glycemic Control; Brown Adipose-tissue; Hepatic Glucose-production; Placebo-controlled Trial
ISSN (print) / ISBN
2040-4603
e-ISSN
2040-4603
Journal
Comprehensive Physiology
Quellenangaben
Volume: 10,
Issue: 1,
Pages: 99-124
Publisher
Wiley
Publishing Place
Oxford
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)