title: Influence of PPAR-alpha agonist fenofibrate on insulin sensitivity and selected adipose tissue-derived hormones in obese women with type 2 diabetes.
abstract: PPAR-alpha agonists improve insulin sensitivity in rodent models of obesity/insulin resistance, but their effects on insulin sensitivity in humans are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-alpha agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group (n=10). No differences were found in serum resistin levels between obese and control group. Fenofibrate treatment decreased serum triglyceride concentrations, while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration. Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment. All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration. We conclude that administration of PPAR-alpha agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-alpha expression in human liver and muscle.
authors.affiliation: Third Department of Medicine, First Faculty of Medicine, Charles University, Praha, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Anderlová
authors.forename: R
authors.initials: R
authors.lastname: Dolezalová
authors.forename: J
authors.initials: J
authors.lastname: Housová
authors.forename: L
authors.initials: L
authors.lastname: Bosanská
authors.forename: D
authors.initials: D
authors.lastname: Haluzíková
authors.forename: J
authors.initials: J
authors.lastname: Kremen
authors.forename: J
authors.initials: J
authors.lastname: Skrha
authors.forename: M
authors.initials: M
authors.lastname: Haluzík
mesh_terms: D054392:Adipokines / Q000097:blood*; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects; D015992:Body Mass Index; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use*; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D009765:Obesity / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D047495:PPAR gamma / Q000819:agonists*; D052243:Resistin / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D054392:Adipokines; D052242:Adiponectin; D001786:Blood Glucose; D008076:Cholesterol, HDL; D011345:Fenofibrate; D006442:Glycated Hemoglobin; D000960:Hypolipidemic Agents; D047495:PPAR gamma; D052243:Resistin; D014280:Triglycerides; C499918:ADIPOQ protein, human; C499624:RETN protein, human