Nutrient Responsive Nesfatin-1 Regulates Energy Balance and Induces Glucose-Stimulated Insulin Secretion in Rats
Nutrient Responsive Nesfatin-1 Regulates Energy Balance and Induces Glucose-Stimulated Insulin Secretion in Rats
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DOI：
10.1210/en.2010-1471
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发表时间：
2011-10-01
期刊：
影响因子：
4.8
通讯作者：
Unniappan, S.
中科院分区：
文献类型：
--
作者：
Gonzalez, R.;Perry, R. L. S.;Unniappan, S.
Nesfatin-1是一种新发现的胰岛β细胞内的神经毒素，我们首次报道了它在胰岛β细胞中的免疫反应。本研究的目的是描述nesfatin-1对全身能量稳态、胰岛素分泌和胰岛素抵抗的影响。在自由采食的雄性Fischer 344大鼠中，检查了使用渗透微泵连续外周递送nesfatin-1对食物摄入和底物分配的体内作用。在离体胰岛中检测nesfatin-1对葡萄糖刺激的胰岛素分泌（GSIS）的作用。使用L 6骨骼肌细胞和分离的大鼠脂肪细胞来评估nesfatin-1对基础和胰岛素介导的葡萄糖摄取以及对这些细胞中胰岛素信号传导的主要步骤的影响。Nesfatin-1减少了累积的食物摄入量，增加了自发的体力活动，全身脂肪氧化和棕色脂肪组织中肉毒碱棕榈酰转移酶I mRNA的表达，但不影响棕色脂肪组织中的解偶联蛋白1 mRNA。在口服葡萄糖耐量试验期间，奈司法丁-1显著增强体内GSIS，并改善胰岛素敏感性。虽然胰岛素刺激的葡萄糖摄取在L 6肌细胞抑制nesfatin-1预处理，基础和胰岛素诱导的葡萄糖摄取脂肪细胞从nesfatin-1处理的大鼠显着增加。与我们的体内结果一致，nesfatin-1增强GSIS从分离的胰岛在正常（5.6 mM）和高（16.7 mM），但不是在低（2 mM），葡萄糖浓度。此外，葡萄糖刺激大鼠胰岛释放nesfatin-1/nucleobindin 2。总的来说，我们的数据表明，葡萄糖响应nesfatin-1调节胰岛素分泌，葡萄糖稳态，和全身能量平衡大鼠。（内分泌学152：3628-3637，2011）
Nesfatin-1 is a recently discovered anorexigen, and we first reported nesfatin-like immunoreactivity in the pancreatic beta-cells. The aim of this study was to characterize the effects of nesfatin-1 on whole-body energy homeostasis, insulin secretion, and glycemia. The in vivo effects of continuous peripheral delivery of nesfatin-1 using osmotic minipumps on food intake and substrate partitioning were examined in ad libitum-fed male Fischer 344 rats. The effects of nesfatin-1 on glucose-stimulated insulin secretion (GSIS) were examined in isolated pancreatic islets. L6 skeletal muscle cells and isolated rat adipocytes were used to assess the effects of nesfatin-1 on basal and insulin-mediated glucose uptake as well as on major steps of insulin signaling in these cells. Nesfatin-1 reduced cumulative food intake and increased spontaneous physical activity, whole-body fat oxidation, and carnitine palmitoyltransferase I mRNA expression in brown adipose tissue but did not affect uncoupling protein 1 mRNAin the brown adipose tissue. Nesfatin-1 significantly enhanced GSIS in vivo during an oral glucose tolerance test and improved insulin sensitivity. Although insulin-stimulated glucose uptake in L6 muscle cells was inhibited by nesfatin-1 pretreatment, basal and insulin-induced glucose uptake in adipocytes from nesfatin-1-treated rats was significantly increased. In agreement with our in vivo results, nesfatin-1 enhanced GSIS from isolated pancreatic islets at both normal (5.6 mM) and high (16.7 mM), but not at low (2 mM), glucose concentrations. Furthermore, nesfatin-1/nucleobindin 2 release from rat pancreatic islets was stimulated by glucose. Collectively, our data indicate that glucose-responsive nesfatin-1 regulates insulin secretion, glucose homeostasis, and whole-body energy balance in rats. (Endocrinology 152: 3628-3637, 2011)