Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes.
Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes.
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DOI：
10.1210/endo.139.2.5716
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发表时间：
1998-02
期刊：
影响因子：
4.8
通讯作者：
Wendy M. Mueller;Francine M. Gregoire;K. Stanhope;Charles V. Mobbs;T. M. Mizuno;Craig H. Warden;Judith S. Stern;P. J. Havel
中科院分区：
文献类型：
--
作者：
Wendy M. Mueller;Francine M. Gregoire;K. Stanhope;Charles V. Mobbs;T. M. Mizuno;Craig H. Warden;Judith S. Stern;P. J. Havel
在人类和啮齿类动物中，从脂肪细胞分泌的循环瘦素与脂肪质量和血浆胰岛素浓度相关。血浆瘦素、胰岛素和葡萄糖在禁食期间减少，在再喂养后增加;然而，调节瘦素分泌变化的潜在机制尚不清楚。为了研究胰岛素刺激的葡萄糖代谢在调节瘦素分泌中的作用，我们研究了胰岛素和葡萄糖转运和代谢抑制剂对原代培养的大鼠脂肪细胞分泌瘦素的影响。胰岛素（0.16-16 nM）在96小时内增加瘦素分泌;然而，瘦素的增加与脂肪细胞摄取的葡萄糖量（r = 0.64; P < 0.0001）比与胰岛素浓度本身（r = 0.20; P < 0.28）更密切相关，表明葡萄糖转运和/或代谢在调节瘦素分泌中的作用。2-脱氧-D-葡萄糖（2-DG）是葡萄糖转运和磷酸化的竞争性抑制剂，在1.6 nM胰岛素存在下，引起浓度依赖性（2-50 mg/dl）的瘦素释放抑制。高浓度葡萄糖可逆转2-DG的抑制作用。葡萄糖转运的另外两种抑制剂根皮素（0.05-0.25 mM）和细胞松弛素-B（0.5-50 μ M）也抑制瘦素分泌。这些药物对瘦素分泌的抑制与对葡萄糖摄取的抑制成正比（r = 0.60 ~ 0.86;均P < 0.01）。糖酵解的两种抑制剂，碘乙酸盐（0.005-1.0 mM）和氟化钠（0.1-5 mM），在1.6 nM胰岛素存在下产生浓度依赖性的瘦素分泌抑制。此外，2-DG和氟化钠均显著降低培养脂肪细胞的瘦素（ob）信使RNA含量，但不影响18 S核糖体RNA含量。我们的结论是，葡萄糖的运输和代谢是重要的因素，在调节瘦素的表达和分泌，胰岛素增加脂肪细胞的葡萄糖利用的效果可能有助于胰岛素刺激的瘦素分泌。因此，在体内，减少脂肪葡萄糖代谢可能是禁食减少循环瘦素的一种机制，而增加脂肪葡萄糖代谢将增加再喂养后的瘦素。
Circulating leptin secreted from adipocytes is correlated with fat mass and plasma insulin concentrations in humans and rodents. Plasma leptin, insulin, and glucose decrease during fasting and increase after refeeding; however, the underlying mechanisms regulating the changes of leptin secretion are not known. To investigate the role of insulin-stimulated glucose metabolism in the regulation of leptin secretion, we examined the effects of insulin and inhibitors of glucose transport and metabolism on leptin secretion from rat adipocytes in primary culture. Insulin (0.16-16 nM) increased leptin secretion over 96 h; however, the increase in leptin was more closely related to the amount of glucose taken up by the adipocytes (r = 0.64; P < 0.0001) than to the insulin concentration per se (r = 0.20; P < 0.28), suggesting a role for glucose transport and/or metabolism in regulating leptin secretion. 2-Deoxy-D-glucose (2-DG), a competitive inhibitor of glucose transport and phosphorylation, caused a concentration-dependent (2-50 mg/dl) inhibition of leptin release in the presence of 1.6 nM insulin. The inhibitory effect of 2-DG was reversed by high concentrations of glucose. Two other inhibitors of glucose transport, phloretin (0.05-0.25 mM) and cytochalasin-B (0.5-50 microM), also inhibited leptin secretion. Inhibition of leptin secretion by these agents was proportional to the inhibition of glucose uptake (r = 0.60 to 0.86; all P < 0.01). Two inhibitors of glycolysis, iodoacetate (0.005-1.0 mM) and sodium fluoride (0.1-5 mM), produced concentration-dependent inhibition of leptin secretion in the presence of 1.6 nM insulin. In addition, both 2-DG and sodium fluoride markedly decreased the leptin (ob) messenger RNA content of cultured adipocytes, but did not affect 18S ribosomal RNA content. We conclude that glucose transport and metabolism are important factors in the regulation of leptin expression and secretion and that the effect of insulin to increase adipocyte glucose utilization is likely to contribute to insulin-stimulated leptin secretion. Thus, in vivo, decreased adipose glucose metabolism may be one mechanism by which fasting decreases circulating leptin, whereas increased adipose glucose metabolism would increase leptin after refeeding.