{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:47:50Z","timestamp":1778687270771,"version":"3.51.4"},"reference-count":37,"publisher":"American Diabetes Association","issue":"8","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,8,1]]},"abstract":"<jats:p>The effects of benfluorex and two of its metabolites (S 422-1 and S 1475-1) on fatty acid and glucose metabolic fluxes and specific gene expression were studied in hepatocytes isolated from 24-h fasted rats. Both benfluorex and S 422-1 (0.1 or 1 mmol\/l) reduced \u03b2-oxidation rates and ketogenesis, whereas S 1475-1 had no effect. At the same concentration, benfluorex and S 422-1 were more efficient in reducing gluconeogenesis from lactate\/pyruvate than S 1475-1. Benfluorex inhibited gluconeogenesis at the level of pyruvate carboxylase (45% fall in acetyl-CoA concentration) and of glyceraldehyde-3-phosphate dehydrogenase (decrease in ATP\/ADP and NAD+\/NADH ratios). Accordingly, neither benfluorex nor S 422-1 inhibited gluconeogenesis from dihydroxyacetone, but both stimulated gluconeogenesis from glycerol. In hepatocytes cultured in the presence of benfluorex or S 422-1 (10 or 100 \u03bcmol\/l), the expression of genes encoding enzymes of fatty acid oxidation (carnitine palmitoyltransferase [CPT] I), ketogenesis (hydroxymethylglutaryl-CoA synthase), and gluconeogenesis (glucose-6-phosphatase, PEPCK) was decreased, whereas mRNAs encoding glucokinase and pyruvate kinase were increased. By contrast, Glut-2, acyl-CoA synthetase, and CPT II gene expression was not affected by benfluorex or S 422-1. In conclusion, this work suggests that benfluorex mainly via S 422-1 reduces gluconeogenesis by affecting gene expression and metabolic status of hepatocytes.<\/jats:p>","DOI":"10.2337\/diabetes.51.8.2363","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2363-2368","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":13,"title":["Effects of Benfluorex on Fatty Acid and Glucose Metabolism in Isolated Rat Hepatocytes"],"prefix":"10.2337","volume":"51","author":[{"given":"Claude","family":"Kohl","sequence":"first","affiliation":[{"name":"Endocrinologie et Me\u0301tabolisme, Institut Cochin, INSERM U567, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Ravel","sequence":"additional","affiliation":[{"name":"Institut de Recherches Internationales Servier, Division Me\u0301tabolisme, Courbevoie, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Girard","sequence":"additional","affiliation":[{"name":"Endocrinologie et Me\u0301tabolisme, Institut Cochin, INSERM U567, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Paul","family":"Pe\u0301gorier","sequence":"additional","affiliation":[{"name":"Endocrinologie et Me\u0301tabolisme, Institut Cochin, INSERM U567, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031206423116000_R1","doi-asserted-by":"crossref","unstructured":"DeFronzo RA, Bonadonna RC, Ferrannini E: Pathogenesis of NIDDM. 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