{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:46:01Z","timestamp":1790858761428,"version":"4.1.0"},"reference-count":119,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Coronary artery disease (CAD), which is the manifestation of atherosclerosis in coronary arteries, is the most common single cause of death and is responsible for disabilities of millions of people worldwide. Despite numerous dedicated clinical studies and an enormous effort to develop diagnostic and therapeutic methods, coronary atherosclerosis remains one of the most serious medical problems of the modern world. Hence, new markers are still being sought to identify and manage CAD optimally. Trying to face this problem, we have raised the question of the most predominant gastrointestinal hormones; glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), mainly involved in carbohydrates disorders, could be also used as new markers of incidence, clinical course, and recurrence of CAD and are related to extent and severity of atherosclerosis and myocardial ischemia. We describe GIP and GLP-1 as expressed in many animal and human tissues, known to be connected to inflammation and related to enormous noncardiac and cardiovascular (CV) diseases. In animals, GIP and GLP-1 improve endothelial function and lead to reduced atherosclerotic plaque macrophage infiltration and stabilize atherosclerotic lesions by directly blocking monocyte migration. Moreover, in humans, GIPR activation induces the pro-atherosclerotic factors ET-1 (endothelin-1) and OPN (osteopontin) but also has anti-atherosclerotic effects through secretion of NO (nitric oxide). Furthermore, four large clinical trials showed a significant reduction in composite of CV death, MI, and stroke in long-term follow-up using GLP-1 analogs for DM 2 patients: liraglutide in LEADER, semaglutide in SUSTAIN-6, dulaglutide in REWIND and albiglutide in HARMONY. However, very little is known about GIP metabolism in the acute phase of myocardial ischemia or for stable patients with CAD, which constitutes a direction for future research. This review aims to comprehensively discuss the impact of GIP and GLP-1 on atherosclerosis and CAD and its potential therapeutic implications.<\/jats:p>","DOI":"10.3390\/biology11020288","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T20:32:30Z","timestamp":1644784350000},"page":"288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Gastrointestinal Incretins\u2014Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-like Peptide-1 (GLP-1) beyond Pleiotropic Physiological Effects Are Involved in Pathophysiology of Atherosclerosis and Coronary Artery Disease\u2014State of the Art"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9230-5455","authenticated-orcid":false,"given":"Szymon","family":"Jonik","sequence":"first","affiliation":[{"name":"Department of Cardiology, Medical University of Warsaw, Banacha 1a Str., 01-267 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Marchel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Warsaw, Banacha 1a Str., 01-267 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Grabowski","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Warsaw, Banacha 1a Str., 01-267 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Opolski","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Warsaw, Banacha 1a Str., 01-267 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3693-8741","authenticated-orcid":false,"given":"Tomasz","family":"Mazurek","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Warsaw, Banacha 1a Str., 01-267 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"ref_1","first-page":"II47","article-title":"Atherosclerotic plaque rupture and thrombosis. Evolving concepts","volume":"82","author":"Fuster","year":"1990","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1111\/j.1582-4934.2012.01552.x","article-title":"Inflammation in atherosclerosis: A cause or a result of vascular disorders?","volume":"16","author":"Manduteanu","year":"2012","journal-title":"J. Cell. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/eurheartj\/ehz425","article-title":"2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes","volume":"41","author":"Knuuti","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1001\/jama.283.24.3223","article-title":"Prevalence, Clinical Characteristics, and Mortality Among Patients with Acute Myocardial Infarction Presenting without Chest Pain","volume":"283","author":"Canto","year":"2000","journal-title":"J. Am. Med. Assoc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1093\/eurheartj\/ehu299","article-title":"Cardiovascular disease in Europe 2014: Epidemiological update","volume":"35","author":"Nichols","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_6","unstructured":"GBD 2019 Diseases and Injuries Collaborators (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 396, 1204\u20131222."},{"key":"ref_7","unstructured":"GBD 2019 Risk Factors Collaborators (2020). Global burden of 87 risk factors in 204 countries and territories, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 396, 1223\u20131249."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019: Update From the GBD 2019 Study","volume":"76","author":"Roth","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1016\/j.jacc.2019.10.009","article-title":"The Global Burden of Cardiovascular Diseases and Risk Factors: 2020 and Beyond","volume":"74","author":"Mensah","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S2213-8587(15)00482-9","article-title":"The incretin effect in healthy individuals and those with type 2 diabetes: Physiology, pathophysiology, and response to therapeutic interventions","volume":"4","author":"Nauck","year":"2016","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1053\/j.gastro.2007.03.054","article-title":"Biology of Incretins: GLP-1 and GIP","volume":"132","author":"Baggio","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.2337\/diabetes.51.9.2757","article-title":"Glucose-Sensing in Glucagon-Like Peptide-1-Secreting Cells","volume":"51","author":"Reimann","year":"2002","journal-title":"Diabetes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.2337\/diabetes.52.5.1147","article-title":"A Novel Glucose-Sensing Mechanism Contributing to Glucagon-Like Peptide-1 Secretion From the GLUTag Cell Line","volume":"52","author":"Gribble","year":"2003","journal-title":"Diabetes"},{"key":"ref_14","first-page":"342","article-title":"Role of prohormone convertases in the tissue-specific processing of proglucagon","volume":"10","author":"Dhanvantari","year":"1996","journal-title":"Mol. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"658","DOI":"10.2337\/diab.42.5.658","article-title":"Biological Effects and Metabolic Rates of Glucagonlike Peptide-1 7-36 Amide and Glucagonlike Peptide-1 7-37 in Healthy Subjects Are Indistinguishable","volume":"42","author":"Wettergren","year":"1993","journal-title":"Diabetes"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11050","DOI":"10.1074\/jbc.M601203200","article-title":"Prohormone Convertase 1\/3 Is Essential for Processing of the Glucose-dependent Insulinotropic Polypeptide Precursor","volume":"281","author":"Ugleholdt","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1210\/endo.133.6.8243312","article-title":"Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain","volume":"133","author":"Usdin","year":"1993","journal-title":"Endocrinology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"609","DOI":"10.2337\/diabetes.50.3.609","article-title":"Reduced Postprandial Concentrations of Intact Biologically Active Glucagon-Like Peptide 1 in Type 2 Diabetic Patients","volume":"50","author":"Krarup","year":"2001","journal-title":"Diabetes"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1113\/jphysiol.1970.sp009155","article-title":"Further purification of a polypeptide demonstrating enterogastrone activity","volume":"209","author":"Brown","year":"1970","journal-title":"J. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14082","DOI":"10.1016\/S0021-9258(18)89859-3","article-title":"Glucagon gene sequence. Four of six exons encode separate functional domains of rat pre-proglucagon","volume":"259","author":"Heinrich","year":"1984","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"611","DOI":"10.2337\/diabetes.49.4.611","article-title":"Effect of glucagon-like peptide1 (7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes","volume":"49","author":"Vella","year":"2000","journal-title":"Diabetes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0140-6736(11)60614-4","article-title":"Type 2 diabetes across generations: From pathophysiology to prevention and management","volume":"378","author":"Nolan","year":"2011","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1172\/JCI111542","article-title":"Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus","volume":"74","author":"Ward","year":"1984","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.2337\/db09-1899","article-title":"Is the Diminished Incretin Effect in Type 2 Diabetes Just an Epi-Phenomenon of Impaired \u03b2-Cell Function?","volume":"59","author":"Meier","year":"2010","journal-title":"Diabetes"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1517\/14656566.7.15.2095","article-title":"Management of Type 2 diabetes: The role of incretin mimetics","volume":"7","author":"Stonehouse","year":"2006","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1172\/JCI116186","article-title":"Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus","volume":"91","author":"Nauck","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"380","DOI":"10.2337\/diabetes.52.2.380","article-title":"The Influence of GLP-1 on Glucose-Stimulated Insulin Secretion: Effects on beta-cell sensitivity in type 2 and nondiabetic subjects","volume":"52","author":"Kjems","year":"2003","journal-title":"Diabetes"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"428","DOI":"10.2337\/dc09-1499","article-title":"Incretin-Based Therapies for the Treatment of Type 2 Diabetes: Evaluation of the Risks and Benefits","volume":"33","author":"Drucker","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1016\/S0140-6736(06)69705-5","article-title":"The incretin system: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes","volume":"368","author":"Drucker","year":"2006","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1111\/j.1742-1241.2009.02086.x","article-title":"Treatment of type 2 diabetes with glucagon-like peptide-1 receptor agonists","volume":"63","author":"Hansen","year":"2009","journal-title":"Int. J. Clin. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.biopha.2018.08.088","article-title":"Recent updates on GLP-1 agonists: Current advancements & challenges","volume":"108","author":"Sharma","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"(2012). American Diabetes Association Standards of Medical Care in Diabetes\u20142012. Diabetes Care, 35, S11\u2013S63.","DOI":"10.2337\/dc12-s011"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"260","DOI":"10.3389\/fendo.2019.00260","article-title":"From the Incretin Concept and the Discovery of GLP-1 to Today\u2019s Diabetes Therapy","volume":"10","author":"Holst","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_34","first-page":"701","article-title":"Suppression of endogenous glucose production by glucagon-like peptide1 independent of islet hormones: An extrapancreatic effect of an incretin hormone","volume":"285","author":"Prigeon","year":"2003","journal-title":"Am. J. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bernsmeier, C., Meyer-Gerspach, A.C., Blaser, L.S., Jeker, L., Steinert, R.E., Heim, M., and Beglinger, C. (2014). Glucose-Induced Glucagon-Like Peptide 1 Secretion Is Deficient in Patients with Non-Alcoholic Fatty Liver Disease. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087488"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1097\/00004872-200306000-00012","article-title":"Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats","volume":"21","author":"Yu","year":"2003","journal-title":"J. Hypertens."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1210\/jc.2003-031403","article-title":"Glucagon-Like Peptide 1 Induces Natriuresis in Healthy Subjects and in Insulin-Resistant Obese Men","volume":"89","author":"Gutzwiller","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/379069a0","article-title":"A role for glucagon-like peptide-1 in the central regulation of feeding","volume":"379","author":"Turton","year":"1996","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1210\/endo.140.1.6421","article-title":"Repeated Intracerebroventricular Administration of Glucagon-Like Peptide-1-(7-36) Amide or Exendin-(9-39) Alters Body Weight in the Rat","volume":"140","author":"Meeran","year":"1999","journal-title":"Endocrinology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.brainres.2005.03.011","article-title":"The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway","volume":"1044","author":"Abbott","year":"2005","journal-title":"Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/nm919","article-title":"Glucagon-like peptide-1 receptor is involved in learning and neuroprotection","volume":"9","author":"During","year":"2003","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1124\/jpet.102.037481","article-title":"Protection and Reversal of Excitotoxic Neuronal Damage by Glucagon-Like Peptide-1 and Exendin-4","volume":"302","author":"Perry","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1523\/JNEUROSCI.4920-04.2005","article-title":"Glucose-Dependent Insulinotropic Polypeptide Is Expressed in Adult Hippocampus and Induces Progenitor Cell Proliferation","volume":"25","author":"Nyberg","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1210\/jcem-55-2-329","article-title":"Gastric Inhibitory Polypeptide Release after Oral Glucose: Relationship to Glucose Intolerance, Diabetes Mellitus, and Obesity","volume":"55","author":"Salera","year":"1982","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/BF00429703","article-title":"Gastric inhibitory polypeptide (GIP) and insulin in obesity: Increased response to stimulation and defective feedback control of serum levels","volume":"14","author":"Creutzfeldt","year":"1978","journal-title":"Diabetologia"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.2337\/diabetes.54.8.2436","article-title":"Chemical Ablation of Gastric Inhibitory Polypeptide Receptor Action by Daily (Pro3)GIP Administration Improves Glucose Tolerance and Ameliorates Insulin Resistance and Abnormalities of Islet Structure in Obesity-Related Diabetes","volume":"54","author":"Gault","year":"2005","journal-title":"Diabetes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1210\/endo.141.3.7366","article-title":"Osteoblast-Derived Cells Express Functional Glucose-Dependent Insulinotropic Peptide Receptors1","volume":"141","author":"Bollag","year":"2000","journal-title":"Endocrinology"},{"key":"ref_48","first-page":"543","article-title":"Effects of glucose-dependent insulinotropic peptide on osteoclast function","volume":"292","author":"Zhong","year":"2007","journal-title":"Am. J. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1007\/s001250050365","article-title":"Failure of GLP-1(7-36)amide to affect glycogenesis in rat skeletal muscle","volume":"38","author":"Ebner","year":"1995","journal-title":"Diabetologia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4445","DOI":"10.1210\/endo.138.10.5270","article-title":"Central Administration of Glucagon-Like Peptide-1 Activates Hypothalamic Neuroendocrine Neurons in the Rat","volume":"138","author":"Larsen","year":"1997","journal-title":"Endocrinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1056\/NEJM199210013271402","article-title":"Gastric Inhibitory Polypeptide-Dependent Cortisol Hypersecretion\u2014A New Cause of Cushing\u2019s Syndrome","volume":"327","author":"Lacroix","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1210\/jc.2011-1508","article-title":"Exenatide Exerts a Potent Antiinflammatory Effect","volume":"97","author":"Chaudhuri","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/jdi.12065","article-title":"Glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1: Incretin actions beyond the pancreas","volume":"4","author":"Seino","year":"2013","journal-title":"J. Diabetes Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.2337\/db14-0100","article-title":"GLP-1 Secretion Is Increased by Inflammatory Stimuli in an IL-6-Dependent Manner, Leading to Hyperinsulinemia and Blood Glucose Lowering","volume":"63","author":"Kahles","year":"2014","journal-title":"Diabetes"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/BF00577838","article-title":"A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-beta-naphthylamide","volume":"7","author":"Glenner","year":"1966","journal-title":"Histochemie"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.2337\/dc13-0496","article-title":"Adipose Dipeptidyl Peptidase-4 and Obesity: Correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro","volume":"36","author":"Sell","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/0-387-32824-6_3","article-title":"Biochemical Properties of Recombinant Prolyl Dipeptidases DPP-IV and DPP8","volume":"575","author":"Chen","year":"2006","journal-title":"Dipeptidyl Aminopeptidases"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.2741\/2787","article-title":"The role of CD26\/dipeptidyl peptidase IV in cancer","volume":"13","author":"Havre","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1161\/CIRCULATIONAHA.111.041418","article-title":"Long-Term Dipeptidyl-Peptidase 4 Inhibition Reduces Atherosclerosis and Inflammation via Effects on Monocyte Recruitment and Chemotaxis","volume":"124","author":"Shah","year":"2011","journal-title":"Circulation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1536\/ihj.19-117","article-title":"Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice","volume":"60","author":"Aini","year":"2019","journal-title":"Int. Heart J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1111\/j.1742-1241.2006.01178.x","article-title":"DPP-4 inhibitors and their potential role in the management of type 2 diabetes","volume":"60","author":"Barnett","year":"2006","journal-title":"Int. J. Clin. Pract."},{"key":"ref_62","first-page":"386","article-title":"DPP4 in diabetes","volume":"6","author":"Wronkowitz","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"286","DOI":"10.2337\/dc17-0280","article-title":"Incretin-Based Therapies and the Short-term Risk of Pancreatic Cancer: Results from Two Retrospective Cohort Studies","volume":"41","author":"Boniol","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12933-021-01344-0","article-title":"CAPTURE: A multinational, cross-sectional study of cardiovascular disease prevalence in adults with type 2 diabetes across 13 countries","volume":"20","author":"Mosenzon","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.2337\/db09-1694","article-title":"Inhibition of Monocyte Adhesion to Endothelial Cells and Attenuation of Atherosclerotic Lesion by a Glucagon-like Peptide-1 Receptor Agonist, Exendin-4","volume":"59","author":"Arakawa","year":"2010","journal-title":"Diabetes"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1007\/s00125-011-2241-2","article-title":"Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice","volume":"54","author":"Nagashima","year":"2011","journal-title":"Diabetologia"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Nogi, Y., Nagashima, M., Terasaki, M., Nohtomi, K., Watanabe, T., and Hirano, T. (2012). Glucose-Dependent Insulinotropic Polypeptide Prevents the Progression of Macrophage-Driven Atherosclerosis in Diabetic Apolipoprotein E-Null Mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035683"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.metabol.2011.11.011","article-title":"Effects of PKF275-055, a dipeptidyl peptidase\u20134 inhibitor, on the development of atherosclerotic lesions in apolipoprotein E\u2013null mice","volume":"61","author":"Terasaki","year":"2012","journal-title":"Metabolism"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.atherosclerosis.2013.08.033","article-title":"Glucagon-like peptide-1 (GLP-1) and its split products GLP-1(9-37) and GLP-1(28-37) stabilize atherosclerotic lesions in ApoE\u2212\/\u2212 mice","volume":"231","author":"Burgmaier","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.molmet.2018.05.014","article-title":"The incretin hormone GIP is upregulated in patients with atherosclerosis and stabilizes plaques in ApoE\u2212\/\u2212 mice by blocking monocyte\/macrophage activation","volume":"14","author":"Kahles","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1210\/en.2018-00336","article-title":"Glucose-Dependent Insulinotropic Polypeptide Suppresses Peripheral Arterial Remodeling in Male Mice","volume":"159","author":"Mori","year":"2018","journal-title":"Endocrinology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2337\/diabetes.54.1.146","article-title":"Glucagon-like Peptide 1 Can Directly Protect the Heart against Ischemia\/Reperfusion Injury","volume":"54","author":"Bose","year":"2005","journal-title":"Diabetes"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1124\/jpet.106.100982","article-title":"Direct Effects of Glucagon-Like Peptide-1 on Myocardial Contractility and Glucose Uptake in Normal and Postischemic Isolated Rat Hearts","volume":"317","author":"Zhao","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.jacc.2008.10.033","article-title":"Exenatide Reduces Infarct Size and Improves Cardiac Function in a Porcine Model of Ischemia and Reperfusion Injury","volume":"53","author":"Timmers","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Lee, T.-M., Chen, W.-T., and Chang, N.-C. (2016). Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats. Biosci. Rep., 36.","DOI":"10.1042\/BSR20150139"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.cmet.2017.11.003","article-title":"Inactivation of the Glucose-Dependent Insulinotropic Polypeptide Receptor Improves Outcomes following Experimental Myocardial Infarction","volume":"27","author":"Ussher","year":"2018","journal-title":"Cell Metab."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1111\/dom.13472","article-title":"Myocardial infarction is sufficient to increase GLP-1 secretion, leading to improved left ventricular contractility and mitochondrial respiratory capacity","volume":"20","author":"Diebold","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.atherosclerosis.2010.04.024","article-title":"One-year treatment with exenatide vs. Insulin Glargine: Effects on postprandial glycemia, lipid profiles, and oxidative stress","volume":"212","author":"Bunck","year":"2010","journal-title":"Atherosclerosis"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/1475-2840-13-49","article-title":"Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study","volume":"13","author":"Rizzo","year":"2014","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12933-020-01014-7","article-title":"Comparison of the effects of twice-daily exenatide and insulin on carotid intima-media thickness in type 2 diabetes mellitus patients: A 52-week randomized, open-label, controlled trial","volume":"19","author":"Zhang","year":"2020","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"697","DOI":"10.2337\/dc10-1949","article-title":"The Possible Protective Role of Glucagon-Like Peptide 1 on Endothelium During the Meal and Evidence for an \u201cEndothelial Resistance\u201d to Glucagon-Like Peptide 1 in Diabetes","volume":"34","author":"Ceriello","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2337\/db15-0122","article-title":"Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB","volume":"65","author":"Berglund","year":"2016","journal-title":"Diabetes"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1161\/01.CIR.0000120505.91348.58","article-title":"Effects of Glucagon-Like Peptide-1 in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction After Successful Reperfusion","volume":"109","author":"Nikolaidis","year":"2004","journal-title":"Circulation"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1093\/eurheartj\/ehr309","article-title":"Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction","volume":"33","author":"Vejlstrup","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1161\/ATVBAHA.113.301586","article-title":"Cardioprotective Effects of Exenatide in Patients With ST-Segment\u2013Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results of exenatide myocardial protection in revascularization study","volume":"33","author":"Woo","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1603827","article-title":"Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1056\/NEJMoa1607141","article-title":"Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0140-6736(19)31149-3","article-title":"Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): A double-blind, randomised placebo-controlled trial","volume":"394","author":"Gerstein","year":"2019","journal-title":"Lancet"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1016\/S0140-6736(18)32261-X","article-title":"Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): A double-blind, randomised placebo-controlled trial","volume":"392","author":"Hernandez","year":"2018","journal-title":"Lancet"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1056\/NEJMoa1901118","article-title":"Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes","volume":"381","author":"Husain","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1056\/NEJMoa1612917","article-title":"Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes","volume":"377","author":"Holman","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1056\/NEJMoa1509225","article-title":"Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome","volume":"373","author":"Pfeffer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1093\/ehjcvp\/pvaa004","article-title":"Glucagon-like peptide-1 receptor agonists and the risk of cardiovascular events in diabetes patients surviving an acute myocardial infarction","volume":"7","author":"Trevisan","year":"2021","journal-title":"Eur. Heart J.-Cardiovasc. Pharmacother."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S2213-8587(17)30412-6","article-title":"Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: A meta-analysis","volume":"6","author":"Bethel","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3346","DOI":"10.1093\/eurheartj\/ehaa082","article-title":"Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: A meta-analysis of randomized controlled trials","volume":"41","author":"Marsico","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.atherosclerosis.2019.07.007","article-title":"Liraglutide in combination with metformin may improve the atherogenic lipid profile and decrease C-reactive protein level in statin treated obese patients with coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial","volume":"288","author":"Anholm","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/XCE.0000000000000011","article-title":"Incretin hormone glucagon-like peptide-1 is increased in patients with acute-phase ST-elevation myocardial infarction treated with a primary percutaneous coronary intervention: A pilot study","volume":"2","author":"Blatt","year":"2013","journal-title":"Cardiovasc. Endocrinol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1093\/eurheartj\/ehz728","article-title":"Glucagon-like peptide 1 levels predict cardiovascular risk in patients with acute myocardial infarction","volume":"41","author":"Kahles","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/dom.13490","article-title":"Endogenous glucagon-like peptide-1 system response is impaired during ST-elevation myocardial infarction in type 2 diabetes patients","volume":"21","author":"Bloch","year":"2019","journal-title":"Diabetes, Obes. Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1042\/CS20110006","article-title":"Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity","volume":"121","author":"Gault","year":"2011","journal-title":"Clin. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00125-018-4810-0","article-title":"Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight\/obese individuals: A randomised, crossover study","volume":"62","author":"Bergmann","year":"2019","journal-title":"Diabetologia"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/dmrr.729","article-title":"Comparison of the anti-diabetic effects of GIP- and GLP-1-receptor activation in obese diabetic (ob\/ob) mice: Studies with DPP IV resistantN-AcGIP and exendin(1-39)amide","volume":"23","author":"Irwin","year":"2007","journal-title":"Diabetes\/Metab. Res. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.regpep.2008.11.007","article-title":"Antidiabetic effects of sub-chronic activation of the GIP receptor alone and in combination with background exendin-4 therapy in high fat fed mice","volume":"153","author":"Irwin","year":"2009","journal-title":"Regul. Pept."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/psc.861","article-title":"Comparison of the subchronic antidiabetic effects of DPP IV\u2013resistant GIP and GLP-1 analogues in obese diabetic (ob\/ob) mice","volume":"13","author":"Irwin","year":"2007","journal-title":"J. Pept. Sci."},{"key":"ref_105","first-page":"912","article-title":"Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at near-physiological insulinotropic hormone and glucose concentrations","volume":"76","author":"Nauck","year":"1993","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0167-0115(94)90136-8","article-title":"The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-37) in normal and diabetic subjects","volume":"51","author":"Elahi","year":"1994","journal-title":"Regul. Pept."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1365-2265.2008.03451.x","article-title":"Effects of peripheral administration of synthetic human glucose-dependent insulinotropic peptide (GIP) on energy expenditure and subjective appetite sensations in healthy normal weight subjects and obese patients with type 2 diabetes","volume":"71","author":"Daousi","year":"2009","journal-title":"Clin. Endocrinol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.2337\/db10-1332","article-title":"GIP Does Not Potentiate the Antidiabetic Effects of GLP-1 in Hyperglycemic Patients With Type 2 Diabetes","volume":"60","author":"Mentis","year":"2011","journal-title":"Diabetes"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Finan, B., Ma, T., Ottaway, N., M\u00fcller, T.D., Habegger, K.M., Heppner, K.M., Kirchner, H., Holland, J., Hembree, J., and Raver, C. (2013). Unimolecular Dual Incretins Maximize Metabolic Benefits in Rodents, Monkeys, and Humans. Sci. Transl. Med., 5.","DOI":"10.1126\/scitranslmed.3007218"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1111\/dom.13024","article-title":"Pharmacodynamics, pharmacokinetics and safety of multiple ascending doses of the novel dual glucose-dependent insulinotropic polypeptide\/glucagon-like peptide-1 agonist RG7697 in people with type 2 diabetes mellitus","volume":"19","author":"Schmitt","year":"2017","journal-title":"Diabetes Obes. Metab."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1016\/S0140-6736(18)32260-8","article-title":"Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: A randomised, placebo-controlled and active comparator-controlled phase 2 trial","volume":"392","author":"Frias","year":"2018","journal-title":"Lancet"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0140-6736(21)01324-6","article-title":"Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): A double-blind, randomised, phase 3 trial","volume":"398","author":"Rosenstock","year":"2021","journal-title":"Lancet"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa2107519","article-title":"Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes","volume":"385","author":"Davies","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S0140-6736(21)01443-4","article-title":"Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): A randomised, open-label, parallel-group, phase 3 trial","volume":"398","author":"Ludvik","year":"2021","journal-title":"Lancet"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1016\/S0140-6736(21)02188-7","article-title":"Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): A randomised, open-label, parallel-group, multicentre, phase 3 trial","volume":"398","author":"Kahn","year":"2021","journal-title":"Lancet"},{"key":"ref_116","unstructured":"(2022, January 12). A Study of Tirzepatide (LY3298176) Versus Placebo in Participants with Type 2 Diabetes Inadequately Controlled on Insulin Glargine with or without Metformin, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04039503."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1093\/eurheartj\/ehz486","article-title":"2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD","volume":"41","author":"Cosentino","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1089\/met.2020.0037","article-title":"Diabetes and the COVID-19 Pandemic: How Insights from Recent Experience Might Guide Future Management","volume":"18","author":"Stoian","year":"2020","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41574-021-00495-0","article-title":"Long COVID\u2014Metabolic risk factors and novel therapeutic management","volume":"17","author":"Khunti","year":"2021","journal-title":"Nat. Rev. Endocrinol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/2\/288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:17:39Z","timestamp":1760134659000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/2\/288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,11]]},"references-count":119,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["biology11020288"],"URL":"https:\/\/doi.org\/10.3390\/biology11020288","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,11]]}}}