Abstract
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 α-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 two 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.
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.
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Gabrielsson BL, Carlsson B, Carlsson LM: Partial genome scale analysis of gene expression in human adipose tissue using DNA array. Obes Res 8: 374–384, 2000
Shi H, Moustaid-Moussa N, Wilkison WO, Zemel MB: Role of the sulfonylurea receptor in regulating human adipocyte metabolism. FASEB J 13: 1833–1838, 1999
Babenko AP, Aguilar-Bryan L, Bryan J: A view of SUR/KIR6.X, KATP channels. Annu Rev Physiol 60: 667–687, 1998
Ashcroft FM, Gribble FM: Correlating structure and function in ATP-sensitive K+ channels. Trends Neurosci 21: 288–294, 1998
Yokoshiki H, Sunagawa M, Seki T, Sperelakis N: ATP-sensitive K+ channels in pancreatic, cardiac, and vascular smooth muscle cells. Am J Physiol 274: C25–C37, 1998
Aguilar-Bryan L, Clement JP, Gonzalez G, Kunjilwar K, Babenko A, Bryan J: Toward understanding the assembly and structure of KATP channels. Physiol Rev 78: 227–245, 1998
Chutkow WA, Makielski JC, Nelson DJ, Burant CF, Fan Z: Alternative splicing of SUR2 Exon 17 regulates nucleotide sensitivity of the ATP-sensitive potassium channel. J Biol Chem 274: 13656–13665, 1999
Chutkow WA, Simon MC, Le Beau MM, Burant CF: Cloning, tissue expression, and chromosomal localization of SUR2, the putative drug-binding subunit of cardiac, skeletal muscle, and vascular KATP channels. Diabetes 45: 1439–1445, 1996
Inagaki N, Gonoi T, Clement JP, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S, Bryan J: Reconstitution of IKATP: An inward rectifier subunit plus the sulfonylurea receptor. Science 270: 1166–1170, 1995
Inagaki N, Inazawa J, Seino S: cDNA sequence, gene structure, and chromosomal localization of the human ATP-sensitive potassium channel, uKATP-1, gene (KCNJ8). Genomics 30: 102–104, 1995
Inagaki N, Gonoi T, Clement JP, Wang CZ, Aguilar-Bryan L, Bryan J, Seino S: A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels. Neuron 16: 1011–1017, 1996
Isomoto S, Kondo C, Yamada M, Matsumoto S, Higashiguchi O, Horio Y, Matsuzawa Y, Kurachi Y: A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel. J Biol Chem 271: 24321–24324, 1996
Pfeifer MA, Halter JB, Graf R, Porte D Jr: Potentiation of insulin secretion to nonglucose stimuli in normal man by tolbutamide. Diabetes 29: 335–340, 1980
Draznin B, Kao M, Sussman KE: Insulin and glyburide increase cytosolic free-Ca2+ concentration in isolated rat adipocytes. Diabetes 36: 174–178, 1987
Xue B, Moustaid N, Wilkison WO, Zemel MB: The agouti gene product inhibits lipolysis in human adipocytes via a Ca2+-dependent mechanism. FASEB J 12: 1391–1396, 1998
Heron L, Virsolvy A, Peyrollier K, Gribble FM, Le Cam A, Ashcroft FM, Bataille D: Human alpha-endosulfine, a possible regulator of sulfonylurea-sensitive KATP channel: Molecular cloning, expression and biological properties. Proc Natl Acad Sci USA 95: 8387–8391, 1998
Smith U, Sjöström L, Björntorp P: Comparison of two methods for determining human adipose cell size. J Lipid Res 13: 822–824, 1972
Russ U, Hambrock A, Artunc F, Loffler-Walz C, Horio Y, Kurachi Y, Quast U: Coexpression with the inward rectifier K(+) channel kir6.1 increases the affinity of the vascular sulfonylurea receptor SUR2B for glibenclamide. Mol Pharmacol 56: 955–961, 1999
Bolinder J, Kager L, Östman J, Arner P: Differences at the receptor and postreceptor levels between human omental and subcutaneous adipose tissue in the action of insulin on lipolysis. Diabetes 32: 117–123, 1983
Zierath JR, Livingston JN, Thorne A, Bolinder J, Reynisdottir S, Lonnqvist F, Arner P: Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: Relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathway. Diabetologia 41: 1343–1354, 1998
Katoh S, Shoici H, Matsushima M, Ikemoto S, Inoue Y, Yokoyama J, Tajima N: Troglitazone prevents the rise in visceral adiposity and improves fatty liver associated with sulfonylurea therapy — a randomized controlled trial. Metabolism 50: 414–417, 2000
Alemzadeh R, Langley G, Upchurch L, Smith P, Slonim AE: Beneficial effect of diazoxide in obese hyperinsulinemic adults. J Clin Endocrinol Metab 83: 1911–1915, 1998
Miura H, Wachtel RE, Loberiza FR Jr, Saito T, Miura M, Nicolosi AC, Gutterman DD: Diabetes mellitus impairs vasodilation to hypoxia in human coronary arterioles: Reduced activity of ATP-sensitive potassium channels. Circ Res 92: 151–158, 2003
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Gabrielsson, B.G., Karlsson, A.C., Lönn, M. et al. Molecular characterization of a local sulfonylurea system in human adipose tissue. Mol Cell Biochem 258, 65–71 (2004). https://doi.org/10.1023/B:MCBI.0000012837.11847.c8
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DOI: https://doi.org/10.1023/B:MCBI.0000012837.11847.c8