title: All-trans retinoic acid lowers serum retinol-binding protein 4 concentrations and increases insulin sensitivity in diabetic mice.
abstract: Recent investigations have demonstrated that elevated serum retinol-binding protein 4 (RBP4) secreted from adipose tissue plays a role in the development of systemic insulin resistance, and lowering RBP4 improves insulin sensitivity. These observations provide a rationale for the development of new antidiabetic agents aimed at reducing serum RBP4 concentrations. In this study, we sought to determine whether retinoic acid (RA) administration decreases serum RBP4 and suppresses insulin resistance in diabetic ob/ob mice. All-trans RA [100 mug/(moused) in corn oil] was administered by stomach intubation to a group of ob/ob mice, with the control group receiving the vehicle for 16 d. Body weight and food intake were monitored. Glucose and insulin tolerance tests were performed. We quantified serum RBP4 and retinol by Western blotting and HPLC, respectively. RA treatment reduced body weight (P < 0.05), basal serum glucose (P < 0.001), serum retinol (P < 0.01), and RBP4 (P < 0.05). It improved insulin sensitivity and decreased the retinol:RBP4 ratio (P < 0.05). These studies suggest that RA is an effective antidiabetic agent that could be considered in the treatment of type 2 diabetes.
authors.affiliation: Laboratory of Nutrition and Cancer, Centre de recherché du Centre hospitalier de l'Université de Montréal-Hôtel-Dieu; Department of Medicine, Université de Montréal, Montreal, H2W 1T7, Canada.
authors.forename: Daniel-Constantin
authors.initials: DC
authors.lastname: Manolescu
authors.forename: Aurelia
authors.initials: A
authors.lastname: Sima
authors.forename: Pangala V
authors.initials: PV
authors.lastname: Bhat
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D051379:Mice; D008820:Mice, Obese; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014801:Vitamin A / Q000097:blood*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; C502487:Rbp4 protein, mouse; D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A; D014212:Tretinoin