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J Clin Endocrinol Metab. 2012 Jul;97(7):E1348-52. doi: 10.1210/jc.2012-1159. Epub 2012 Apr 24.

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.

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  • 1Medical Research Laboratories, Aarhus University Hospital, 8000 Aarhus C, Denmark. tsn@farm.au.dk

Abstract

CONTEXT:

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.

DESIGN AND PARTICIPANTS:

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.

SETTING:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00653510.

[PubMed - indexed for MEDLINE]
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