title: Pioglitazone Therapy Increases Insulin-Stimulated Release of d-Chiro-Inositol-Containing Inositolphosphoglycan Mediator in Women with Polycystic Ovary Syndrome.
abstract: Insulin resistance in women with polycystic ovary syndrome (PCOS) may be mediated, in part, by a deficiency in the insulin-stimulated release of a d-chiro-inositol-inositolphosphoglycan (DCI-IPG) mediator of insulin action. Supporting this idea, several studies have reported improved insulin sensitivity in both lean and obese women with PCOS after oral administration of DCI. Pioglitazone improves insulin sensitivity in women with PCOS, but it is unknown whether this may be contributed by enhanced insulin-stimulated release of the DCI-IPG second messenger. The study aimed to determine if pioglitazone increases release of biologically active DCI-IPG per unit insulin released during an oral glucose tolerance test (OGTT).
  
  
  
  A randomized, double-blind placebo-controlled trial was conducted in 32 women with PCOS at a tertiary referral center in Venezuela. The intervention comprised administration of pioglitazone 45 mg daily or matched placebo for 6 months. Outcome measures included area under curves (AUC) of DCI-IPG (AUCDCI-IPG), insulin (AUCinsulin), and the ratio of AUCDCI-IPGto AUCinsulinduring a 2-hr OGTT.
  
  
  
  After treatment with pioglitazone, AUCinsulinduring the OGTT decreased and whole body insulin sensitivity, as determined by the Matsuda index, increased significantly only in the pioglitazone group. The ratio of AUCDCI-IPG/AUCinsulinincreased in the pioglitazone group by 1.85-fold (P < 0.0001) with no significant change in the placebo group. Change in Matsuda index correlated with change in DCI-IPG released per unit of insulin during OGTT (r = 0.47, P < 0.01).
  
  
  
  In women with PCOS, pioglitazone increased insulin-stimulated release of the DCI-IPG second messenger of insulin action, which may contribute to its insulin-sensitizing effect in these women.
authors.affiliation: 1 Department of Pediatrics, Virginia Commonwealth University , Richmond, Virginia.
authors.forename: Anshu
authors.initials: A
authors.lastname: Gupta
authors.affiliation: 2 Department of Internal Medicine, Obesity, Diabetes and Fertility Unit, Hospital de Clinicas Caracas, Central University of Venezuela , Caracas, Venezuela .|3 Diabetes Unit, Wolfson Medical Center, Sackler Faculty of Medicine, Tel Aviv University , Holon, Israel .
authors.forename: Daniela
authors.initials: D
authors.lastname: Jakubowicz
authors.affiliation: 4 Department of Internal Medicine, Virginia Commonwealth University , Richmond, Virginia.
authors.forename: John E
authors.initials: JE
authors.lastname: Nestler
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007295:Inositol Phosphates / Q000097:blood* / Q000172:deficiency; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007329:Insulin Antagonists / Q000097:blood; D007333:Insulin Resistance; D000077205:Pioglitazone; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000188:drug therapy*; D011134:Polysaccharides / Q000097:blood* / Q000172:deficiency; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D007295:Inositol Phosphates; D007328:Insulin; D007329:Insulin Antagonists; D011134:Polysaccharides; D045162:Thiazolidinediones; C028039:inositol phosphate glycan; D000077205:Pioglitazone