Peroxisome proliferator-activated receptor (PPAR)-alpha activation prevents diabetes in OLETF rats: comparison with PPAR-gamma activation.
Lipid accumulation in nonadipose tissues is closely related to the development of type 2 diabetes in obese subjects. We examined the potential preventive effect of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma stimulation on the development of diabetes in obese diabetes-prone OLETF rats. Chronic administration of a PPAR-alpha agonist (0.5% [wt/wt] fenofibrate) or a PPAR-gamma agonist (3 mg x kg(-1) x day(-1) rosiglitazone) completely prevented the development of glycosuria. Pancreatic islets from untreated OLETF rats underwent sequential hypertrophy and atrophy, which was completely prevented by chronic fenofibrate treatment. In contrast, rosiglitazone treatment did not affect islet hypertrophy at earlier stages but prevented beta-cell atrophy at later stages. Fenofibrate treatment decreased body weight and visceral fat, whereas rosiglitazone treatment increased body weight. Despite the opposite effects on adiposity, both drugs were equally effective in improving insulin actions in skeletal muscle. Furthermore, both drugs significantly decreased the triglyceride content in the soleus muscle and pancreatic islets. The present study demonstrates that the PPAR-alpha agonist fenofibrate prevents the development of diabetes in OLETF rats by reducing adiposity, improving peripheral insulin action, and exerting beneficial effects on pancreatic beta-cells.
Koh
Eun Hee
EH
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea.
Kim
Min-Seon
MS
Park
Joong-Yeol
JY
Kim
Hyun Sik
HS
Youn
Ji-Young
JY
Park
Hye-Sun
HS
Youn
Jang Hyun
JH
Lee
Ki-Up
KU
D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D005227:Fatty Acids / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D006003:Glycogen / Q000096:biosynthesis; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity; D051381:Rats; D020334:Rats, Inbred OLETF; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D014781:Viscera
D001786:Blood Glucose; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014280:Triglycerides; D000077154:Rosiglitazone; D006003:Glycogen; D011345:Fenofibrate