Molecular characterization of a local sulfonylurea system in human adipose tissue.
Artikel i vetenskaplig tidskrift, 2004

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.

Inwardly Rectifying

Drug

Obesity

metabolism

Receptors

metabolism

metabolism

genetics

Peptides

genetics

genetics

metabolism

Diet Therapy

metabolism

Adipose Tissue

Potassium Channels

metabolism

Middle Aged

Female

ATP-Binding Cassette Transporters

Weight Loss

Humans

metabolism

Potassium Channels

genetics

genetics

Författare

Britt Gabrielsson

Göteborgs universitet

A Cecilia Karlsson

Göteborgs universitet

Malin Lönn

Göteborgs universitet

Louise Olofsson

Göteborgs universitet

Jenny Palming

Göteborgs universitet

Jarl S Torgerson

Göteborgs universitet

Lars Sjöström

Göteborgs universitet

Björn Carlsson

Göteborgs universitet

Staffan Edén

Göteborgs universitet

Lena M S Carlsson

Göteborgs universitet

Molecular and Cellular Biochemistry

0300-8177 (ISSN) 1573-4919 (eISSN)

Vol. 258 65-71

Ämneskategorier

Endokrinologi och diabetes

Fysiologi

MEDICIN OCH HÄLSOVETENSKAP

PubMed

15030171