Molecular characterization of a local sulfonylurea system in human adipose tissue.
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.
Gabrielsson
Britt G
BG
Research Centre for Endocrinology and Metabolism, Department of Internal Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. britt.gabrielsson@medic.gu.se
Karlsson
A Cecilia
AC
Lönn
Malin
M
Olofsson
Louise E
LE
Johansson
Jenny M
JM
Torgerson
Jarl S
JS
Sjöström
Lars
L
Carlsson
Björn
B
Edén
Staffan
S
Carlsson
Lena M S
LM
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D004035:Diet Therapy; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D054086:KATP Channels; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D064233:Sulfonylurea Receptors; D015431:Weight Loss; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D036341:Intercellular Signaling Peptides and Proteins; D054086:KATP Channels; D010455:Peptides; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human; C577510:ABCC9 protein, human; C075663:endosulfine; C092520:uK-ATP-1 potassium channel