Role of calcium in the secretion of leptin from white adipocytes
Role of calcium in the secretion of leptin from white adipocytes
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DOI：
10.1152/ajpregu.00368.2004
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发表时间：
2004-12-01
影响因子：
2.8
通讯作者：
Bukowiecki, LJ
中科院分区：
文献类型：
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作者：
Cammisotto, PG;Bukowiecki, LJ
在从大鼠白色脂肪组织分离的脂肪细胞中研究钙调节瘦素分泌的机制。在含有葡萄糖但不含钙的培养基中孵育脂肪细胞，显著抑制胰岛素刺激的瘦素分泌（ISLS）和合成，而不影响基础瘦素分泌或脂解。然而，当丙酮酸被用作底物时，ISLS对钙的缺乏不敏感。同样，在葡萄糖存在下，根皮素、细胞松弛素B和W- 13（3种干扰葡萄糖代谢早期步骤的药物）可完全阻止胰岛素的刺激作用，但在丙酮酸存在下则不能。因此，钙似乎是葡萄糖利用所特别需要的。另一方面，Ca-45摄取和瘦素分泌不受胰岛素或L-型钙通道抑制剂的影响。然而，增加质膜对钙渗透性的药物（高钙浓度、A- 23187和ATP）增加了Ca-45摄取，同时抑制了ISLS。类似地，毒胡萝卜素释放内源性钙储备以剂量依赖性方式抑制ISLS。ATP，A- 23187，钙，和毒胡萝卜素抑制ISLS，即使在丙酮酸的存在下。这些结果表明：1）细胞外钙是ISLS所必需的，主要是通过影响葡萄糖摄取，2）胰岛素不影响细胞外钙摄取，3）通过刺激其摄取或其从内源性储存中释放来增加细胞溶质钙，从而在不依赖于葡萄糖代谢的水平上抑制ISLS。因此，钙调节瘦素从脂肪细胞分泌的方式是显着不同的，它的作用在许多其他多肽激素的胞吐。
The mechanism by which calcium regulates leptin secretion was studied in adipocytes isolated from rat white adipose tissue. Incubation of adipocytes in a medium containing glucose, but no calcium, markedly inhibited insulin- stimulated leptin secretion ( ISLS) and synthesis, without affecting basal leptin secretion or lipolysis. However, when pyruvate was used as a substrate, ISLS was insensitive to the absence of calcium. Likewise, the stimulatory effects of insulin were completely prevented by phloretin, cytochalasin B, and W- 13 ( 3 agents that interfere with early steps of glucose metabolism) in the presence of glucose, but not in the presence of pyruvate. Thus calcium appears to be specifically required for glucose utilization. On the other hand, Ca-45 uptake and leptin secretion were not affected by insulin or by inhibitors of L- type calcium channels. However, agents increasing plasma membrane permeability to calcium ( high calcium concentrations, A- 23187, and ATP) increased Ca-45 uptake and concomitantly inhibited ISLS. Similarly, release of endogenous calcium stores by thapsigargin inhibited ISLS in a dose- dependent manner. ATP, A- 23187, calcium, and thapsigargin inhibited ISLS, even in the presence of pyruvate. These results show that 1) extracellular calcium is necessary for ISLS, mainly by affecting glucose uptake, 2) insulin does not affect extracellular calcium uptake, and 3) increasing cytosolic calcium by stimulating its uptake or its release from endogenous stores inhibits ISLS at a level independent of glucose metabolism. Thus calcium regulates leptin secretion from adipocytes in a manner that is markedly different from its role in the exocytosis of many other polypeptidic hormones.