title: Pioglitazone treatment enhances the sympathetic nervous system response to oral carbohydrate load in obese individuals with metabolic syndrome.
abstract: BACKGROUND
  Insulin resistance is associated with blunted sympathetic nervous system (SNS) response to carbohydrate ingestion which may contribute to postprandial hypotension and impaired body weight homeostasis.
  
  
  OBJECTIVE
  This study was conducted to examine the effects of pharmacological insulin sensitization on whole-body norepinephrine kinetics during a standard 75-g oral glucose tolerance test (OGTT) in obese, insulin resistant subjects with metabolic syndrome.
  
  
  METHODS
  Un-medicated individuals (n=42, mean age 56±0.8 yrs, body mass index 34±0.6 kg/m(2)) were randomised to 12-weeks pioglitazone (PIO, 15 mg for 6 weeks, then 30 mg daily) or placebo using a double-blind, parallel group design. Whole-body norepinephrine kinetics (arterial norepinephrine concentration, calculated spillover and clearance rates), spontaneous cardiac baroreflex sensitivity, heart rate and blood pressure were measured at times 0, 30, 60, 90 and 120 minutes during OGTT. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp (M) and Matsuda index.
  
  
  RESULTS
  PIO increased clamp derived glucose utilisation by 35% (P<0.001) and there were concurrent reductions in inflammatory status and plasma triglycerides (P<0.05). Fasting norepinephrine kinetic parameters were unaltered. PIO treatment was associated with lower plasma insulin incursions, greater reduction in diastolic blood pressure and enhanced baroreflex sensitivity during OGTT (P all <0.05). The overall norepinephrine spillover response (AUC(0-120)) increased significantly in the PIO group (group × time interaction, P=0.04), with greatest increment at 30 minutes post-glucose (101±38 ng/min at baseline versus 241±48 ng/min post treatment, P=0.04) and correlated with percent improvement in M.
  
  
  CONCLUSIONS
  PIO enhances the early postprandial SNS response to carbohydrate ingestion.
authors.affiliation: Laboratory of Human Neurotransmitters, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia. Electronic address: Nora.Straznicky@bakeridi.edu.au.
authors.forename: Nora E
authors.initials: NE
authors.lastname: Straznicky
authors.affiliation: Laboratory of Human Neurotransmitters, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Mariee T
authors.initials: MT
authors.lastname: Grima
authors.affiliation: Laboratory of Human Neurotransmitters, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Carolina I
authors.initials: CI
authors.lastname: Sari
authors.affiliation: Laboratory of Human Neurotransmitters, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Nina
authors.initials: N
authors.lastname: Eikelis
authors.affiliation: Laboratory of Human Neurotransmitters, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Faculty of Medicine, Nursing and Health Sciences, Melbourne, Victoria, Australia.
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Lambert
authors.affiliation: Laboratory of Cardiovascular Nutrition, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Nestel
authors.affiliation: Laboratory of Human Neurotransmitters, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Katrina
authors.initials: K
authors.lastname: Richards
authors.affiliation: Laboratory of Human Neurotransmitters, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Department of Primary Health Care, Monash University, Melbourne, Victoria, Australia.
authors.forename: John B
authors.initials: JB
authors.lastname: Dixon
authors.affiliation: Laboratory of Neurovascular Hypertension & Kidney Disease, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Faculty of Medicine, Nursing and Health Sciences, Melbourne, Victoria, Australia; Department of Physiology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Markus P
authors.initials: MP
authors.lastname: Schlaich
authors.affiliation: Laboratory of Human Neurotransmitters, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia; Department of Physiology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Lambert
mesh_terms: D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002241:Carbohydrates / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test / Q000379:methods; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology*; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D000077205:Pioglitazone; D013564:Sympathetic Nervous System / Q000187:drug effects*; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D002241:Carbohydrates; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D005947:Glucose; D000077205:Pioglitazone; D009638:Norepinephrine
keywords: Insulin resistance; Metabolic syndrome; Norepinephrine; Pioglitazone; Sympathetic nervous system