a Department of Medical Sciences, Clinical Diabetes and Metabolism , Uppsala University , Uppsala , Sweden.
b Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory , Uppsala University , Uppsala , Sweden.
Adipocyte. 2018;7(4):285-296. doi: 10.1080/21623945.2018.1503030. Epub 2018 Aug 14.
The protective mechanisms of peroxisome proliferator-activated receptor gamma (PPARγ) Pro12Ala polymorphism in type 2 diabetes (T2D) are unclear. We obtained subcutaneous adipose tissue (AT) before and 3 h after oral glucose (OGTT) in carriers and non-carriers of the Ala allele (12 Pro/Pro, 15 Pro/Ala, and 13 Ala/Ala). Adipogenesis, adipocyte glucose uptake and lipolysis as well as PPARγ target gene expression were investigated and compared between the genotype groups. During fasting and post-OGTT, neither basal nor insulin-stimulated adipocyte glucose uptake differed between genotypes. Compared to fasting, a decreased hormone-sensitive lipase gene expression in Pro/Pro (p < 0.05) was accompanied with a higher antilipolytic effect of insulin post-OGTT (p < 0.01). The adipocyte size was similar across groups. Preadipocyte differentiation rates between Pro/Pro and Ala/Ala were unchanged. In conclusion, no major differences in AT differentiation, glucose uptake, lipolysis or expression of PPARγ target genes were observed between different PPARγ Pro12Ala genotypes. Albeit small, our study may suggest that other pathways in AT or effects exerted in other tissues might contribute to the Pro12Ala-mediated protection against T2D.
过氧化物酶体增殖物激活受体 γ（PPARγ）Pro12Ala 多态性在 2 型糖尿病（T2D）中的保护机制尚不清楚。我们在 Ala 等位基因（12 Pro/Pro、15 Pro/Ala 和 13 Ala/Ala）携带者和非携带者中获得了口服葡萄糖耐量试验（OGTT）前后的皮下脂肪组织（AT）。研究并比较了不同基因型组的脂肪生成、脂肪细胞葡萄糖摄取和脂肪分解以及 PPARγ 靶基因表达。在禁食和 OGTT 后，基因型之间的基础和胰岛素刺激的脂肪细胞葡萄糖摄取均无差异。与禁食相比，Pro/Pro 中激素敏感脂肪酶基因表达降低（p<0.05），OGTT 后胰岛素的抗脂肪分解作用增强（p<0.01）。各组的脂肪细胞大小相似。Pro/Pro 和 Ala/Ala 之间的前脂肪细胞分化率没有变化。总之，不同的 PPARγ Pro12Ala 基因型之间，AT 分化、葡萄糖摄取、脂肪分解或 PPARγ 靶基因的表达没有明显差异。尽管很小，但我们的研究可能表明，AT 中的其他途径或在其他组织中产生的影响可能有助于 Pro12Ala 介导的对 T2D 的保护。
