{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:01:06Z","timestamp":1791928866761,"version":"4.3.4"},"reference-count":57,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"14","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2025,11,3]]},"DOI":"10.1167\/iovs.66.14.4","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:00:51Z","timestamp":1762174851000},"page":"4","source":"Crossref","is-referenced-by-count":1,"title":["Dipeptidyl Peptidase 4, a Novel Adipokine, Impairs Retinal Microcirculation in Patients With Type 2 Diabetes Mellitus"],"prefix":"10.1167","volume":"66","author":[{"given":"Tsuneaki","family":"Omae","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Kamiya","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Otani","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harumasa","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiji","family":"Nagaoka","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"461S","DOI":"10.1093\/ajcn\/83.2.461S","article-title":"Obesity and the role of adipose tissue in inflammation and metabolism","volume":"83","author":"Greenberg","year":"2006","journal-title":"Am J Clin Nutr"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"4586","DOI":"10.1167\/iovs.13-11756","article-title":"Adiponectin-induced dilation of isolated porcine retinal arterioles via production of nitric oxide from endothelial cells","volume":"54","author":"Omae","year":"2013","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"4143","DOI":"10.1167\/iovs.15-16447","article-title":"Relationship between retinal blood flow and serum adiponectin concentrations in patients with type 2 diabetes mellitus","volume":"56","author":"Omae","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.2337\/db10-1707","article-title":"Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome","volume":"60","author":"Lamers","year":"2011","journal-title":"Diabetes"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1097\/IAE.0000000000001098","article-title":"Protective effects of dipeptidyl peptidase-4 inhibitors on progression of diabetic retinopathy in patients with type 2 diabetes","volume":"36","author":"Chung","year":"2016","journal-title":"Retina"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1007\/s00125-005-1749-8","article-title":"Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus","volume":"48","author":"Mannucci","year":"2005","journal-title":"Diabetologia"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"328","DOI":"10.5301\/ejo.5000547","article-title":"Circulating dipeptidyl peptidase-4 activity is associated with diabetic retinopathy in type 1 diabetic patients","volume":"25","author":"Blaslov","year":"2015","journal-title":"Eur J Ophthalmol"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"6729","DOI":"10.1167\/iovs.10-5364","article-title":"Impaired retinal circulation in patients with type 2 diabetes mellitus: retinal laser Doppler velocimetry study","volume":"51","author":"Nagaoka","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"Suppl 1","key":"bib9","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.2337\/diacare.26.2007.S5","article-title":"Report of the expert committee on the diagnosis and classification of diabetes mellitus","volume":"26","author":"Expert Committee on the Diagnosis and Classification of Diabetes Mellitus","year":"2003","journal-title":"Diabetes Care"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1001\/jama.289.19.2560","article-title":"The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report","volume":"289","author":"Chobanian","year":"2003","journal-title":"JAMA"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"45","DOI":"10.5551\/jat.14.45","article-title":"Executive summary of Japan Atherosclerosis Society (JAS) guideline for diagnosis and prevention of atherosclerotic cardiovascular diseases for Japanese","volume":"14","author":"Teramoto","year":"2007","journal-title":"J Atheroscler Thromb"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1053\/j.ajkd.2008.12.034","article-title":"Revised equations for estimated GFR from serum creatinine in Japan","volume":"53","author":"Matsuo","year":"2009","journal-title":"Am J Kidney Dis"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1111\/j.1523-1755.2005.00365.x","article-title":"Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO)","volume":"67","author":"Levey","year":"2005","journal-title":"Kidney Int"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"957","DOI":"10.2337\/dc12-0864","article-title":"Relationship between retinal blood flow and renal function in patients with type 2 diabetes and chronic kidney disease","volume":"36","author":"Nagaoka","year":"2013","journal-title":"Diabetes Care"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/S0161-6420(84)34336-6","article-title":"Diabetic retinopathy. Assessment of severity and progression","volume":"91","author":"Klein","year":"1984","journal-title":"Ophthalmology"},{"issue":"5 Suppl","key":"bib16","first-page":"786","article-title":"Grading diabetic retinopathy from stereoscopic color fundus photographs\u2013an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group","volume":"98","author":"[No authors listed].","year":"1991","journal-title":"Ophthalmology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1167\/iovs.05-0218","article-title":"Noninvasive evaluation of wall shear stress on retinal microcirculation in humans","volume":"47","author":"Nagaoka","year":"2006","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib18","first-page":"3037","article-title":"The effect of nitric oxide on retinal blood flow during hypoxia in cats","volume":"43","author":"Nagaoka","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1167\/iovs.04-1438","article-title":"Requisite roles of A2A receptors, nitric oxide, and KATP channels in retinal arteriolar dilation in response to adenosine","volume":"46","author":"Hein","year":"2005","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1167\/iovs.05-1224","article-title":"Dilation of retinal arterioles in response to lactate: role of nitric oxide, guanylyl cyclase, and ATP-sensitive potassium channels","volume":"47","author":"Hein","year":"2006","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1167\/iovs.06-0856","article-title":"Simvastatin elicits dilation of isolated porcine retinal arterioles: role of nitric oxide and mevalonate-rho kinase pathways","volume":"48","author":"Nagaoka","year":"2007","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"6749","DOI":"10.1167\/iovs.10-6826","article-title":"Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, induces dilation of isolated porcine retinal arterioles: role of nitric oxide and potassium channels","volume":"52","author":"Omae","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib23","first-page":"H1063","article-title":"Endothelium-dependent, flow-induced dilation of isolated coronary arterioles","volume":"259","author":"Kuo","year":"1990","journal-title":"Am J Physiol"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.exer.2009.07.019","article-title":"Effect of aging on retinal circulation in normotensive healthy subjects","volume":"89","author":"Nagaoka","year":"2009","journal-title":"Exp Eye Res"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"e43518","DOI":"10.1371\/journal.pone.0043518","article-title":"Serum carcinoembryonic antigen is associated with abdominal visceral fat accumulation in female Korean nonsmokers","volume":"7","author":"Lee","year":"2012","journal-title":"PLoS One"},{"key":"bib26","doi-asserted-by":"publisher","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":"bib27","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/1475-2840-12-125","article-title":"Advanced glycation end products evoke endothelial cell damage by stimulating soluble dipeptidyl peptidase-4 production and its interaction with mannose 6-phosphate\/insulin-like growth factor II receptor","volume":"12","author":"Ishibashi","year":"2013","journal-title":"Cardiovasc Diabetol"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"2172","DOI":"10.1002\/oby.20833","article-title":"DPP4 inhibition attenuates filtration barrier injury and oxidant stress in the Zucker obese rat","volume":"22","author":"Nistala","year":"2014","journal-title":"Obesity (Silver Spring)"},{"key":"bib29","first-page":"5","article-title":"Endothelial modulation of arteriolar tone","volume":"7","author":"Kuo","year":"1992","journal-title":"News Physiol Sci"},{"key":"bib30","first-page":"H14","article-title":"Adaptive regulation of wall shear stress to flow change in the canine carotid artery","volume":"239","author":"Kamiya","year":"1980","journal-title":"Am J Physiol"},{"key":"bib31","first-page":"H326","article-title":"Corelease of nitric oxide and prostaglandins mediates flow-dependent dilation of rat gracilis muscle arterioles","volume":"267","author":"Koller","year":"1994","journal-title":"Am J Physiol"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/S0022-3565(25)25081-9","article-title":"Endothelium-dependent gender differences in the response of the rat pulmonary artery to the thromboxane mimic (U46619)","volume":"237","author":"Cunard","year":"1986","journal-title":"J Pharmacol Exp Ther"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1016\/S0022-3565(25)38636-2","article-title":"Influence of gender on vascular reactivity in the rat","volume":"268","author":"Li","year":"1994","journal-title":"J Pharmacol Exp Ther"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S0024-3205(96)00663-7","article-title":"Gender differences in the generation of superoxide anions in the rat aorta","volume":"60","author":"Brandes","year":"1997","journal-title":"Life Sci"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1161\/hq0302.104515","article-title":"Greater oxidative stress in healthy young men compared with premenopausal women","volume":"22","author":"Ide","year":"2002","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"936","DOI":"10.7326\/0003-4819-121-12-199412150-00005","article-title":"Estrogen improves endothelium-dependent, flow-mediated vasodilation in postmenopausal women","volume":"121","author":"Lieberman","year":"1994","journal-title":"Ann Intern Med"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"e0168190","DOI":"10.1371\/journal.pone.0168190","article-title":"Ocular blood flow measurements in healthy White subjects using laser speckle flowgraphy","volume":"11","author":"Luft","year":"2016","journal-title":"PLoS One"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1001\/archopht.124.5.665","article-title":"Effect of systemic administration of simvastatin on retinal circulation","volume":"124","author":"Nagaoka","year":"2006","journal-title":"Arch Ophthalmol"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"592760","DOI":"10.1155\/2010\/592760","article-title":"Effects of sitagliptin treatment on dysmetabolism, inflammation, and oxidative stress in an animal model of type 2 diabetes (ZDF rat)","volume":"2010","author":"Ferreira","year":"2010","journal-title":"Mediators Inflamm"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1097\/FJC.0b013e31826be204","article-title":"Dipeptidyl peptidase-4 inhibition with saxagliptin enhanced nitric oxide release and reduced blood pressure and sICAM-1 levels in hypertensive rats","volume":"60","author":"Mason","year":"2012","journal-title":"J Cardiovasc Pharmacol"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1007\/s12325-012-0045-5","article-title":"Effects on lipid profile of dipeptidyl peptidase 4 inhibitors, pioglitazone, acarbose, and sulfonylureas: meta-analysis of placebo-controlled trials","volume":"29","author":"Monami","year":"2012","journal-title":"Adv Ther"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1016\/j.bbadis.2014.04.013","article-title":"Dipeptidyl peptidase-IV inhibition prevents blood-retinal barrier breakdown, inflammation and neuronal cell death in the retina of type 1 diabetic rats","volume":"1842","author":"Goncalves","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1159\/000354116","article-title":"Beneficial effects of vildagliptin on retinal injury in obese type 2 diabetic rats","volume":"50","author":"Maeda","year":"2013","journal-title":"Ophthalmic Res"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1111\/j.1463-1326.2011.01548.x","article-title":"Protective effects of the dipeptidyl peptidase IV inhibitor sitagliptin in the blood-retinal barrier in a type 2 diabetes animal model","volume":"14","author":"Goncalves","year":"2012","journal-title":"Diabetes Obes Metab"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/1475-2840-12-59","article-title":"Vildagliptin in addition to metformin improves retinal blood flow and erythrocyte deformability in patients with type 2 diabetes mellitus - results from an exploratory study","volume":"12","author":"Berndt-Zipfel","year":"2013","journal-title":"Cardiovasc Diabetol"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.vph.2011.03.001","article-title":"Acute DPP-4 inhibition modulates vascular tone through GLP-1 independent pathways","volume":"55","author":"Shah","year":"2011","journal-title":"Vascul Pharmacol"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.3390\/ijms25031829","article-title":"Association of DPP-4 concentrations with the occurrence of gestational diabetes mellitus and excessive gestational weight gain","volume":"25","author":"Niebrzydowska-Tatus","year":"2024","journal-title":"Int J Mol Sci"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"e0140618","DOI":"10.1371\/journal.pone.0140618","article-title":"Serum levels of soluble CD26\/dipeptidyl peptidase-IV in type 2 diabetes mellitus and its association with metabolic syndrome and therapy with antidiabetic agents in Malaysian subjects","volume":"10","author":"Ahmed","year":"2015","journal-title":"PLoS One"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"4143","DOI":"10.1167\/iovs.15-16447","article-title":"Relationship between retinal blood flow and serum adiponectin concentrations in patients with type 2 diabetes mellitus","volume":"56","author":"Omae","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.2174\/0929867323666160405111354","article-title":"Effect of dipeptidyl peptidase-4 inhibitors on plasma adiponectin: a systematic review and meta-analysis of randomized controlled trials","volume":"23","author":"Sahebkar","year":"2016","journal-title":"Curr Med Chem"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.2337\/db22-0219","article-title":"Retinal oxygen metabolism in patients with type 2 diabetes and different stages of diabetic retinopathy","volume":"71","author":"Hommer","year":"2022","journal-title":"Diabetes"},{"key":"bib52","first-page":"1140","article-title":"Retinal blood flow changes in type I diabetes. A long-term follow-up study","volume":"37","author":"Konno","year":"1996","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.bbrc.2004.09.021","article-title":"Reduced serum dipeptidyl peptidase-IV after metformin and pioglitazone treatments","volume":"324","author":"Lenhard","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1111\/j.1464-5491.2005.01461.x","article-title":"Inhibition of dipeptidyl peptidase IV activity by oral metformin in type 2 diabetes","volume":"22","author":"Lindsay","year":"2005","journal-title":"Diabet Med"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.1210\/jc.2012-4288","article-title":"CD26\/DPP4 levels in peripheral blood and T cells in patients with type 2 diabetes mellitus","volume":"98","author":"Lee","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"3766","DOI":"10.1038\/s41467-020-17556-z","article-title":"Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans","volume":"11","author":"Baggio","year":"2020","journal-title":"Nat Commun"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"446","DOI":"10.3109\/02713683.2012.654883","article-title":"Association between diabetic retinopathy and flow-mediated vasodilation in type 2 DM","volume":"37","author":"Sogawa","year":"2012","journal-title":"Curr Eye Res"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2811033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:32:04Z","timestamp":1791927124000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2811033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":57,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2025,11,3]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.66.14.4","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11,3]]}}}