title: Effect of the combination of metformin and fenofibrate on glucose homeostasis in diabetic Goto-Kakizaki rats.
abstract: Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-α-dependent manner. We investigated whether a PPARα agonist, fenofibrate, exhibits an additive or synergistic effect on glucose metabolism, independent of its lipid-lowering effect, when added to metformin. Non-obese diabetic Goto-Kakizaki (GK) rats were divided into four groups and treated for 28 days with metformin, fenofibrate, metformin plus fenofibrate or vehicle. The random blood glucose levels, body weights, food intake and serum lipid profiles were not significantly different among the groups. After 4 weeks, metformin, but not fenofibrate, markedly reduced the blood glucose levels during oral glucose tolerance tests, and this effect was attenuated by adding fenofibrate. Metformin increased the expression of the GLP-1 receptor in pancreatic islets, whereas fenofibrate did not. During the intraperitoneal glucose tolerance tests with the injection of a GLP-1 analog, metformin and/or fenofibrate did not alter the insulin secretory responses. In conclusion, fenofibrate did not confer any beneficial effect on glucose homeostasis but reduced metformin's glucose-lowering activity in GK rats, thus discouraging the addition of fenofibrate to metformin to improve glycemic control.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae Jung
authors.initials: TJ
authors.lastname: Oh
authors.forename: Ji Yon
authors.initials: JY
authors.lastname: Shin
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Young Min
authors.initials: YM
authors.lastname: Cho
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005247:Feeding Behavior / Q000187:drug effects; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D008687:Metformin; D000077270:Exenatide; D005947:Glucose; D011345:Fenofibrate