title: Reduced mRNA and protein expression of perilipin A and G0/G1 switch gene 2 (G0S2) in human adipose tissue in poorly controlled type 2 diabetes.
abstract: BACKGROUND
  Increased lipolysis and free fatty acid (FFA) levels contribute significantly to the pathogenesis of chronic and acute insulin resistance in type 2 diabetes, but the underlying mechanisms are uncertain.
  
  
  OBJECTIVE
  Our objective was to test whether increased lipolysis and FFA levels induced by insulin withdrawal are accompanied by increased adipose tissue (AT) contents of adipose triglyceride lipase (ATGL) and/or altered intracellular ATGL regulation.
  
  
  METHODS
  Nine patients with type 2 diabetes were examined twice in a randomized crossover design after 16 h of 1) hyperglycemia/insulin withdrawal and 2) euglycemia/insulin infusion. Blood samples were drawn and a sc abdominal AT biopsy was obtained.
  
  
  METHODS
  The study was conducted at a university hospital research unit.
  
  
  RESULTS
  Circulating glucose (7.2 ± 0.3 vs. 11.2 ± 0.8 mmol/liter) and FFA (0.51 ± 0.05 vs. 0.65 ± 0.04 mmol/liter) were increased and insulin levels decreased after insulin withdrawal. AT ATGL protein tended to be increased (P = 0.075) after insulin withdrawal; by contrast, AT protein and mRNA content of perilipin A (Plin) and G(0)/G(1) switch gene 2 (G0S2), known negative regulators of ATGL activity, were decreased by 20-30% (all P values <0.03). All measured parameters related to hormone-sensitive lipase remained unaffected.
  
  
  CONCLUSIONS
  We found reduced mRNA and protein content of Plin and G0S2 and borderline increased ATGL protein in sc AT from poorly controlled type 2 diabetic subjects. This suggests that increased ATGL activity may contribute to the elevated lipolysis and circulating FFA levels in acute insulin withdrawal and metabolic dysregulation in type 2 diabetic patients and that this mechanism may be modifiable.
authors.affiliation: Medical Research Laboratories, Aarhus University Hospital, 8000 Aarhus C, Denmark. tsn@farm.au.dk
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Nielsen
authors.forename: Ulla
authors.initials: U
authors.lastname: Kampmann
authors.forename: Roni R
authors.initials: RR
authors.lastname: Nielsen
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.forename: Lotte
authors.initials: L
authors.lastname: Orskov
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Jens O
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: Sten
authors.initials: S
authors.lastname: Lund
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D007332:Insulin Infusion Systems; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000217:Acyltransferases
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D008049:Lipase; D000070778:Perilipin-1; D010750:Phosphoproteins; D012333:RNA, Messenger; C508073:G0S2 protein, human; C494794:PNPLA2 protein, human; D000217:Acyltransferases