Shi H, Moustaid-Moussa N, Wilkison W O, Zemel M B
Department of Nutrition, The University of Tennessee, Knoxville, Tennessee 37996, USA.
FASEB J. 1999 Oct;13(13):1833-8. doi: 10.1096/fasebj.13.13.1833.
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 microM) increases in [Ca2+]i (P<0.05). Similarly, glibenclamide (10 microM) 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 microM) 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.
细胞内钙离子（[Ca2+]i）在脂肪细胞脂肪生成、脂肪分解和甘油三酯积累中的调节作用已得到证实。作用于胰腺磺脲类受体（SUR）以增加（如格列本脲）或降低（如二氮嗪）[Ca2+]i的化合物会导致体重增加相应地增加和减少。然而，这些体重增加和减轻的作用归因于胰岛素释放，而非这些化合物对脂肪细胞SUR及其相关ATP敏感性钾通道（K(ATP)通道）的直接作用。因此，我们评估了人类脂肪细胞SUR在调节脂肪细胞代谢中的直接作用。我们使用针对SUR1高度保守区域的引物进行逆转录聚合酶链反应（RT-PCR），以证明人类脂肪细胞表达SUR1。通过序列分析确认PCR产物，并将其用作探针，通过Northern印迹分析证明脂肪细胞SUR1的表达。脂肪细胞对格列本脲呈现剂量依赖性（0 - 20 microM）的[Ca2+]i增加（P<0.05）。同样，格列本脲（10 microM）使脂肪细胞脂肪酸合酶活性增加67%（P<0.001），使3-磷酸甘油脱氢酶活性增加48%（P<0.01），并使脂肪分解抑制68%（P<0.01），而二氮嗪（10 microM）完全阻断了这些作用。这些数据表明，人类脂肪细胞表达一种调节[Ca2+]i的SUR，从而对脂肪生成和脂肪分解发挥协同控制作用。因此，脂肪细胞SUR1可能是肥胖治疗干预开发的一个重要靶点。
