HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by SHI, H. Articles by ZEMEL, M. B. Search for Related Content PubMed PubMed Citation Articles by SHI, H. Articles by ZEMEL, M. B.

Role of the sulfonylurea receptor in regulating human adipocyte metabolism

HANG SHI^*, NAIMA MOUSTAID-MOUSSA^*, W. O. WILKISON and MICHAEL B. ZEMEL^*1

^* Department of Nutrition, The University of Tennessee, Knoxville, Tennessee 37996, USA; and
Zen-Bio, Inc., Research Triangle Park, North Carolina 27709, USA

¹Correspondence: University of Tennessee, 1215 West Cumberland Avenue, #229, Knoxville, TN 37996-1900, USA. E-mail: mzemel{at}utk.edu

A regulatory role for intracellular Ca²⁺ ([Ca²⁺]_i) in adipocyte lipogenesis, lipolysis and triglyceride accumulation has been demonstrated. Compounds acting on the pancreatic sulfonylurea receptor (SUR) to increase (e.g., glibenclamide) or decrease (e.g., diazoxide) [Ca²⁺]_i cause corresponding increases and decreases in weight gain. However, these weight gain and loss effects have been attributed to insulin release rather than to the primary effects of these compounds on the adipocyte SUR and its associated K_ATP channel. Accordingly, we have evaluated the direct role of the human adipocyte SUR in regulating adipocyte metabolism. We used RT-PCR with primers for a highly conserved region of SUR1 to demonstrate that human adipocytes express SUR1. The PCR product was confirmed by sequence analysis and used as a probe to demonstrate adipocyte SUR1 expression by Northern blot analysis. Adipocytes exhibited glibenclamide dose-responsive (0–20 µM) increases in [Ca²⁺]_i (P<0.05). Similarly, glibenclamide (10 µM) caused a 67% increase in adipocyte fatty acid synthase activity (P<0.001), a 48% increase in glycerol-3-phosphate dehydrogenase activity (P<0.01) and a 68% inhibition in lipolysis (P<0.01), whereas diazoxide (10 µM) completely prevented each of these effects. These data demonstrate that human adipocytes express a SUR that regulates [Ca²⁺]_i and, consequently, exerts coordinate control over lipogenesis and lipolysis. Accordingly, the adipocyte SUR1 may represent an important target for the development of therapeutic interventions in obesity.—Shi, H., Moustaid-Moussa, N., Wilkison, W. O., Zemel, M. B. Role of the sulfonylurea receptor in regulating human adipocyte metabolism.

Key Words: adipocytes • intracellular Ca²⁺ • fatty acid synthase • SUR

This article has been cited by other articles:

				N. Nakano, N. Miyazawa, T. Sakurai, T. Kizaki, K. Kimoto, K. Takahashi, H. Ishida, M. Takahashi, K. Suzuki, and H. Ohno Gliclazide Inhibits Proliferation but Stimulates Differentiation of White and Brown Adipocytes J. Biochem., November 1, 2007; 142(5): 639 - 645. [Abstract] [Full Text] [PDF]

				T. Ren, J. He, H. Jiang, L. Zu, S. Pu, X. Guo, and G. Xu Metformin reduces lipolysis in primary rat adipocytes stimulated by tumor necrosis factor-{alpha} or isoproterenol. J. Mol. Endocrinol., August 1, 2006; 37(1): 175 - 183. [Abstract] [Full Text] [PDF]

				H. Shi, B. Cave, K. Inouye, C. Bjorbaek, and J. S. Flier Overexpression of Suppressor of Cytokine Signaling 3 in Adipose Tissue Causes Local but Not Systemic Insulin Resistance Diabetes, March 1, 2006; 55(3): 699 - 707. [Abstract] [Full Text] [PDF]

				M. B. Zemel The Role of Dairy Foods in Weight Management J. Am. Coll. Nutr., December 1, 2005; 24(suppl_6): 537S - 546S. [Abstract] [Full Text] [PDF]

				X. Sun and M. B. Zemel Calcium and Dairy Products Inhibit Weight and Fat Regain during Ad Libitum Consumption Following Energy Restriction in Ap2-Agouti Transgenic Mice J. Nutr., November 1, 2004; 134(11): 3054 - 3060. [Abstract] [Full Text] [PDF]

				M. B Zemel Role of calcium and dairy products in energy partitioning and weight management Am. J. Clinical Nutrition, May 1, 2004; 79(5): 907S - 912S. [Abstract] [Full Text] [PDF]

				M. B. Zemel Mechanisms of Dairy Modulation of Adiposity J. Nutr., January 1, 2003; 133(1): 252S - 256. [Abstract] [Full Text] [PDF]

				M. Ozata, D. Gungor, M. Turan, G. Ozisik, N. Bingol, T. Ozgurtas, and I. C. Ozdemir Improved Glycemic Control Increases Fasting Plasma Acylation-Stimulating Protein and Decreases Leptin Concentrations in Type II Diabetic Subjects J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3659 - 3664. [Abstract] [Full Text] [PDF]

				R. S. Surwit, T. M. Dixon, A. E. Petro, K. W. Daniel, and S. Collins Diazoxide Restores {beta}3-Adrenergic Receptor Function in Diet-Induced Obesity and Diabetes Endocrinology, October 1, 2000; 141(10): 3630 - 3637. [Abstract] [Full Text] [PDF]

				M. STANDRIDGE, R. ALEMZADEH, M. ZEMEL, J. KOONTZ, and N. MOUSTAID-MOUSSA Diazoxide down-regulates leptin and lipid metabolizing enzymes in adipose tissue of Zucker rats FASEB J, March 1, 2000; 14(3): 455 - 460. [Abstract] [Full Text]