Preventive effects of fenofibrate on insulin resistance, hyperglycaemia, visceral fat accumulation in NIH mice induced by small-dose streptozotocin and lard.
High-fat diets and oxidative damage may contribute to the development of type 2 diabetes. Hypolipidaemic drugs and antioxidants were supposed to prevent the development of the disease. In this study, we investigated preventive effects of fenofibrate (200 mg kg(-1)), vitamin C (30 mg kg(-1)), combination of both in mice induced by streptozotocin (35 mg kg(-1)) and soluble lard (15 ml kg(-1)). The results showed the mice demonstrated hyperglycaemia and hypercholesterolaemia, visceral fat accumulation, and a slight increase in liver glycogen/triglyceride and oxidative stress within 60 days of treatment. Fenofibrate enhanced insulin sensitivity, improved glycaemic control, lowered serum triglycerides, reduced body and visceral fat weights, and decreased liver glycogen/lipid levels but showed hepatotoxicity in the mice. Vitamin C neither itself prevented nor enhanced preventive effects of fenofibrate on glucose and lipid metabolism but partly attenuated the hepatotoxicity of fenofibrate. These results suggest that fenofibrate inhibit development of type 2 diabetes induced by high-fat diets and oxidative stress. However, here, vitamin C just can serve as an adjunct to fenofibrate therapy against its hepatotoxicity. In the future study, we should investigate if higher dosage of vitamin C or other antioxidants would enhance preventive effects of fenofibrate in type 2 diabetes.
Xie
Weidong
W
Life Sciences Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China.
Nie
Yong
Y
Du
Lijun
L
Zhang
Yaou
Y
Cai
Guoping
G
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D004041:Dietary Fats; D004359:Drug Therapy, Combination; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D006003:Glycogen / Q000378:metabolism; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D013311:Streptozocin; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D000975:Antioxidants; D001786:Blood Glucose; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D014280:Triglycerides; D013311:Streptozocin; D006003:Glycogen; D002784:Cholesterol; D020780:Matrix Metalloproteinase 9; D001205:Ascorbic Acid; C029310:lard; D011345:Fenofibrate