Obese subjects with type 2 diabetes had lower glucose disposal (4.9 vs 7.5 mg/min/kg; P<0.001) and significantly lower expression of adipogenic genes including SREBP1c (P<0.01) than obese controls.
Cross-Sectional (n=67)
Obese subjects with type 2 diabetes exhibit decreased expression of specific adipogenic genes in subcutaneous adipose tissue, which may contribute to impaired adipogenesis, larger fat cells, and insulin resistance.
p-value: p=<0.01
OBJECTIVE: Our objective was to delineate the potential role of adipogenesis in insulin resistance and type 2 diabetes. Obesity is characterized by an increase in adipose tissue mass resulting from enlargement of existing fat cells (hypertrophy) and/or from increased number of adipocytes (hyperplasia). The inability of the adipose tissue to recruit new fat cells may cause ectopic fat deposition and insulin resistance. RESEARCH METHODS AND PROCEDURES: We examined the expression of candidate genes involved in adipocyte proliferation and/or differentiation CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPdelta, GATA domain-binding protein 3 (GATA3), C/EBPbeta, peroxisome proliferator-activated receptor (PPAR) gamma2, signal transducer and activator of transcription 5A (STAT5A), Wnt-10b, tumor necrosis factor alpha, sterol regulatory element-binding protein 1c (SREBP1c), 11 beta-hydroxysteroid dehydrogenase, PPARG angiopoietin-related protein (PGAR), insulin-like growth factor 1, PPARgamma coactivator 1alpha, PPARgamma coactivator 1beta, and PPARdelta in subcutaneous adipose tissue from 42 obese individuals with type 2 diabetes and 25 non-diabetic subjects matched for age and obesity. RESULTS: Insulin sensitivity was measured by a 3-hour 80 mU/m2 per minute hyperinsulinemic glucose clamp (100 mg/dL). As expected, subjects with type 2 diabetes had lower glucose disposal (4.9 +/- 1.9 vs. 7.5 +/- 2.8 mg/min per kilogram fat-free mass; p < 0.001) and larger fat cells (0.90 +/- 0.26 vs. 0.78 +/- 0.17 microm; p = 0.04) as compared with obese control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and PPARgamma2, p = 0.02) had significantly lower expression in obese type 2 diabetics, whereas C/EBPbeta only tended to be lower (p = 0.07). DISCUSSION: This cross-sectional study supports the hypothesis that impaired expression of adipogenic genes may result in impaired adipogenesis, potentially leading to larger fat cells in subcutaneous adipose tissue and insulin resistance.
Dubois et al. (Fri,) conducted a cross-sectional in Obesity with type 2 diabetes (n=67). Type 2 diabetes vs. Non-diabetic obese controls was evaluated on Expression of adipogenic genes (SREBP1c, STAT5A, and PPARgamma2) (p=<0.01). Obese subjects with type 2 diabetes had lower glucose disposal (4.9 vs 7.5 mg/min/kg; P<0.001) and significantly lower expression of adipogenic genes including SREBP1c (P<0.01) than obese controls.