Exp Mol Med.  2013 Jul;45(7):e30.

Effect of the combination of metformin and fenofibrate on glucose homeostasis in diabetic Goto-Kakizaki rats

• Oh TJ
• Shin JY
• Kang GH
• Park KS
• Cho YM

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)-alpha-dependent manner. We investigated whether a PPARalpha 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.

Keyword

fenofibrate; glucagon-like peptide-1; Goto-Kakizaki rats; metformin; peroxisome proliferator-activated receptor alpha

MeSH Terms

Animals
Blood Glucose/metabolism
Body Weight/drug effects
Diabetes Mellitus, Experimental/*drug therapy/*metabolism
Drug Therapy, Combination
Feeding Behavior/drug effects
Fenofibrate/*pharmacology/therapeutic use
Glucagon-Like Peptide 1/agonists/metabolism
Glucose/*metabolism
Glucose Tolerance Test
Homeostasis/*drug effects
Immunohistochemistry
Injections, Intraperitoneal
Insulin-Secreting Cells/drug effects/metabolism/pathology
Lipid Metabolism/drug effects
Male
Metformin/*pharmacology/therapeutic use
Peptides/administration & dosage/pharmacology
Rats
Receptors, Glucagon/metabolism
Venoms/administration & dosage/pharmacology
Blood Glucose
Fenofibrate
Glucagon-Like Peptide 1
Glucose
Metformin
Peptides
Receptors, Glucagon
Venoms