title: The incretin system ABCs in obesity and diabetes - novel therapeutic strategies for weight loss and beyond.
abstract: Incretins are gastrointestinal-derived hormones released in response to a meal playing a key role in the regulation of postprandial secretion of insulin (incretin effect) and glucagon by the pancreas. Both incretins, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1), have several other actions by peripheral and central mechanisms. GLP-1 regulates body weight by inhibiting appetite and delaying gastric, emptying actions that are dependent on central nervous system GLP-1 receptor activation. Several other hormones and gut peptides, including leptin and ghrelin, interact with GLP-1 to modulate appetite. GLP-1 is rapidly degraded by the multifunctional enzyme dipeptidyl peptidase-4 (DPP-4). DPP-4 is involved in adipose tissue inflammation, which is associated with insulin resistance and diabetes progression, being a common pathophysiological mechanism in obesity-related complications. Furthermore, the incretin system appears to provide the basis for understanding the high weight loss efficacy of bariatric surgery, a widely used treatment for obesity, often in association with diabetes. The present review brings together new insights into obesity pathogenesis, integrating GLP-1 and DPP-4 in the complex interplay between obesity and inflammation, namely, in diabetic patients. This in turn will provide the basis for novel incretin-based therapeutic strategies for obesity and diabetes with promising benefits in addition to weight loss. © 2016 World Obesity.
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine and Center for Neuroscience and Cell Biology - Institute for Biomedical Imaging and Life Sciences (CNC.IBILI) Research Consortium, University of Coimbra, Coimbra, Portugal.
authors.forename: A L
authors.initials: AL
authors.lastname: João
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine and Center for Neuroscience and Cell Biology - Institute for Biomedical Imaging and Life Sciences (CNC.IBILI) Research Consortium, University of Coimbra, Coimbra, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Reis
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine and Center for Neuroscience and Cell Biology - Institute for Biomedical Imaging and Life Sciences (CNC.IBILI) Research Consortium, University of Coimbra, Coimbra, Portugal.
authors.forename: R
authors.identifier: 0000-0001-7828-2296
authors.initials: R
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000628:therapy*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004195:Disease Models, Animal; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D009765:Obesity / Q000628:therapy*; D015431:Weight Loss
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: Bariatric surgery; incretins; obesity; type-2 diabetes mellitus (T2DM)