{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:25:17Z","timestamp":1787495117421,"version":"build-2736575974"},"reference-count":42,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":3843,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>The incidence of high dietary carbohydrate-induced type 2 diabetes is increasing worldwide. Methylglyoxal (MG) is a reactive glucose metabolite and a major precursor of advanced glycation end products (AGEs). MG levels are elevated in diabetic patients. We investigated the effects of chronic administration of MG on glucose tolerance and \u03b2-cell insulin secreting mechanism in 12-week-old male Sprague-Dawley rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>MG (60 mg\/kg\/day) or 0.9% saline was administered by continuous infusion with a minipump for 28 days. We performed glucose and insulin tolerance tests and measured adipose tissue glucose uptake and insulin secretion from isolated pancreatic islets. We also used cultured INS-1E cells, a pancreatic \u03b2-cell line, for molecular studies. Western blotting, quantitative PCR, immunohistochemistry, and transferase-mediated dUTP nick-end labeling (TUNEL) assay were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In rats treated with MG and MG + l-buthionine sulfoximine (BSO), MG levels were significantly elevated in plasma, pancreas, adipose tissue, and skeletal muscle; fasting plasma glucose was elevated, whereas insulin and glutathione were reduced. These two groups also had impaired glucose tolerance, reduced GLUT-4, phosphoinositide-3-kinase activity, and insulin-stimulated glucose uptake in adipose tissue. In the pancreatic \u03b2-cells, MG and MG + BSO reduced insulin secretion, pancreatic duodenal homeobox-1, MafA, GLUT-2, and glucokinase expression; increased C\/EBP\u03b2, nuclear factor-\u03baB, MG-induced AGE, N\u03b5-carboxymeythyllysine, and receptor for AGEs expression; and caused apoptosis. Alagebrium, an MG scavenger and an AGE-breaking compound, attenuated the effects of MG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Chronic MG induces biochemical and molecular abnormalities characteristic of type 2 diabetes and is a possible mediator of high carbohydrate-induced type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db10-0627","type":"journal-article","created":{"date-parts":[[2011,2,7]],"date-time":"2011-02-07T22:45:47Z","timestamp":1297118747000},"page":"899-908","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":133,"title":["Chronic Methylglyoxal Infusion by Minipump Causes Pancreatic \u03b2-Cell Dysfunction and Induces Type 2 Diabetes in Sprague-Dawley Rats"],"prefix":"10.2337","volume":"60","author":[{"given":"Arti","family":"Dhar","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indu","family":"Dhar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaushik M.","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, 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