title: Skeletal muscle uncoupling protein-3 restores upon intervention in the prediabetic and diabetic state: implications for diabetes pathogenesis?
abstract: OBJECTIVE
  Skeletal muscle uncoupling protein-3 (UCP3) is reduced in type 2 diabetes, and in the pre-diabetic condition of impaired glucose tolerance (IGT). Here we examined whether intervention programs known to improve insulin sensitivity are paralleled by an increase in skeletal muscle UCP3 protein levels.
  
  
  METHODS
  Skeletal muscle UCP3 protein content was measured before and after one year of an exercise intervention in muscle biopsies of eight diabetic subjects. In addition, UCP3 was measured in IGT subjects before and after 1 year of following a lifestyle-intervention program or serving as control.
  
  
  RESULTS
  In the diabetic patients a significant increase of approximately 75% in UCP3 protein was found after 1 year of exercise training (P < 0.05). In IGT subjects UCP3 protein increased in the intervention group (P = 0.02), while UCP3 remained unaltered in the control group (P = 0.64).
  
  
  CONCLUSIONS
  Both, exercise training and a lifestyle-intervention program increase UCP3 protein content in skeletal muscle of subjects with reduced glycaemic control, indicating a restoration towards normal UCP3 levels. These data support the idea that UCP3 has a role in the aetiology of type 2 diabetes mellitus.
authors.affiliation: Department of Human Biology, Nutrition and Toxicology Research Institute NUTRIM, Maastricht University, Maastricht, The Netherlands. m.mensink@hb.unimaas.nl
authors.forename: M
authors.initials: M
authors.lastname: Mensink
authors.forename: M K C
authors.initials: MK
authors.lastname: Hesselink
authors.forename: L B
authors.initials: LB
authors.lastname: Borghouts
authors.forename: H
authors.initials: H
authors.lastname: Keizer
authors.forename: E
authors.initials: E
authors.lastname: Moonen-Kornips
authors.forename: G
authors.initials: G
authors.lastname: Schaart
authors.forename: E E
authors.initials: EE
authors.lastname: Blaak
authors.forename: P
authors.initials: P
authors.lastname: Schrauwen
mesh_terms: D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D045786:Diterpenes, Kaurane / Q000494:pharmacology; D015444:Exercise; D005951:Glucose Tolerance Test; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D011236:Prediabetic State / Q000378:metabolism*; D000071247:Uncoupling Protein 3
chemical_list: D001786:Blood Glucose; D045786:Diterpenes, Kaurane; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; C515747:isosteviol