{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:12:31Z","timestamp":1793412751350,"version":"4.5.0"},"reference-count":85,"publisher":"American Diabetes Association","issue":"suppl_3","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,12,1]]},"abstract":"<jats:p>\u03b2-Cells possess inherent mechanisms to adapt to overnutrition and the prevailing concentrations of glucose, fatty acids, and other fuels to maintain glucose homeostasis. However, this is balanced by potentially harmful actions of the same nutrients. Both glucose and fatty acids may cause good\/adaptive or evil\/toxic actions on the \u03b2-cell, depending on their concentrations and the time during which they are elevated. Chronic high glucose dramatically influences \u03b2-cell lipid metabolism via substrate availability, changes in the activity and expression of enzymes of glucose and lipid metabolism, and modifications in the expression level of key transcription factors. We discuss here the emerging view that \u03b2-cell \u201cglucotoxicity\u201d is in part indirectly caused by \u201clipotoxicity,\u201d and that \u03b2-cell abnormalities will become particularly apparent when both glucose and circulating fatty acids are high. We support the concept that elevated glucose and fatty acids synergize in causing toxicity in islets and other organs, a process that may be instrumental in the pleiotropic defects associated with the metabolic syndrome and type 1 and type 2 diabetes. The mechanisms by which hyperglycemia and hyperlipidemia alter insulin secretion are discussed and a model of \u03b2-cell \u201cglucolipotoxicity\u201d that implicates alterations in \u03b2-cell malonyl-CoA concentrations; peroxisome proliferator-activated receptor-\u03b1 and -\u03b3 and sterol regulatory element binding protein-1c expression; and lipid partitioning is proposed.<\/jats:p>","DOI":"10.2337\/diabetes.51.2007.s405","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"S405-S413","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":359,"title":["Malonyl-CoA Signaling, Lipid Partitioning, and Glucolipotoxicity"],"prefix":"10.2337","volume":"51","author":[{"given":"Marc","family":"Prentki","sequence":"first","affiliation":[{"name":"From the Molecular Nutrition Unit, Department of Nutrition, University of Montreal, the Centre de Recherche du CHUM, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Joly","sequence":"additional","affiliation":[{"name":"From the Molecular Nutrition Unit, Department of Nutrition, University of Montreal, the Centre de Recherche du CHUM, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wissal","family":"El-Assaad","sequence":"additional","affiliation":[{"name":"From the Molecular Nutrition Unit, Department of Nutrition, University of Montreal, the Centre de Recherche du CHUM, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphae\u0308l","family":"Roduit","sequence":"additional","affiliation":[{"name":"From the Molecular Nutrition Unit, Department of Nutrition, University of Montreal, the Centre de Recherche du CHUM, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031208003332300_R1","doi-asserted-by":"crossref","unstructured":"Kahn CR: Insulin action, diabetogenes, and the cause of type 2 diabetes. 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