Gabrielsson Britt G, Karlsson A Cecilia, Lönn Malin, Olofsson Louise E, Johansson Jenny M, Torgerson Jarl S, Sjöström Lars, Carlsson Björn, Edén Staffan, Carlsson Lena M S
Research Centre for Endocrinology and Metabolism, Department of Internal Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Mol Cell Biochem. 2004 Mar;258(1-2):65-71. doi: 10.1023/b:mcbi.0000012837.11847.c8.
ATP-sensitive potassium (KATP) channels are present in many cell types and link cellular metabolism to the membrane potential. These channels are heterooctamers composed of two subunits. The sulfonylurea receptor (SUR) subunits are targets for drugs that are inhibitors or openers of the KATP channels, while the inwardly rectifying K+ (Kir) subunits form the ion channel. Two different SUR genes (SUR1 and SUR2) and two different Kir6.x genes (Kir6.1 and Kir6.2) have been identified. In addition, isoforms of SUR2, SUR2A and SUR2B, have been described. We have previously performed expression profiling on pooled human adipose tissue and found high expression of SUR2. Others have reported expression of SUR1 in human adipocytes. The aim of this study was to characterize the expression of the sulfonylurea receptor complex components in human adipose tissue. RT-PCR analysis, verified by restriction enzyme digestions and DNA sequencing, showed that SUR2B, Kir6.1 and alpha-endosulfine, but not SUR1, SUR2A or Kir6.2, are expressed in human adipose tissue. Real-time RT-PCR showed that SUR2B was expressed at higher levels in subcutaneous compared with omental adipose tissue in paired biopsies obtained from seven obese men (p < 0.05). Analysis of tissue distribution showed that SUR2B expression in adipose tissue was lower than that in muscle, similar to that in heart and liver, while the expression in pancreas was lower. The effect of caloric restriction was tested in obese men (n = 10) treated with very low calorie diet for 16 weeks, followed by a gradual reintroduction of ordinary food for 2 weeks. Biopsies were taken at week 0, 8 and 18. There was no consistent effect of weight reduction on SUR2B or Kir6.1 expression. We conclude that the necessary components for a local sulfonylurea system are expressed in human adipose tissue and that the sulfonylurea receptor complex in this tissue is composed of SUR2B and Kir6.1. The expression of SUR2B was higher in subcutaneous compared with omental adipose tissue and was not affected by weight loss.
ATP敏感性钾（KATP）通道存在于多种细胞类型中，将细胞代谢与膜电位联系起来。这些通道是由两个亚基组成的异源八聚体。磺脲类受体（SUR）亚基是KATP通道抑制剂或开放剂药物的作用靶点，而内向整流钾离子（Kir）亚基形成离子通道。已鉴定出两种不同的SUR基因（SUR1和SUR2）以及两种不同的Kir6.x基因（Kir6.1和Kir6.2）。此外，还描述了SUR2的亚型SUR2A和SUR2B。我们之前对人脂肪组织样本进行了表达谱分析，发现SUR2表达水平很高。其他人报道过人脂肪细胞中SUR1的表达。本研究的目的是鉴定人脂肪组织中磺脲类受体复合物成分的表达情况。经限制性内切酶消化和DNA测序验证的逆转录聚合酶链反应（RT-PCR）分析表明，人脂肪组织中表达的是SUR2B、Kir6.1和α-内硫素，而不是SUR1、SUR2A或Kir6.2。实时RT-PCR显示，在从7名肥胖男性获取的配对活检样本中，皮下脂肪组织中SUR2B的表达水平高于网膜脂肪组织（p < 0.05）。组织分布分析表明，脂肪组织中SUR2B的表达低于肌肉组织，与心脏和肝脏中的表达水平相似，而胰腺中的表达更低。对10名肥胖男性进行了热量限制效果测试，他们接受极低热量饮食治疗16周，随后逐渐重新引入普通食物2周。在第0、8和18周采集活检样本。体重减轻对SUR2B或Kir6.1的表达没有一致的影响。我们得出结论，人脂肪组织中表达了局部磺脲类系统的必需成分，该组织中的磺脲类受体复合物由SUR2B和Kir6.1组成。皮下脂肪组织中SUR2B的表达高于网膜脂肪组织，且不受体重减轻的影响。
