Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration
Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration
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DOI：
10.1007/s00125-008-0944-9
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发表时间：
2008-05-01
期刊：
影响因子：
8.2
通讯作者：
Kadowaki, T.
中科院分区：
文献类型：
--
作者：
Okamoto, M.;Ohara-Imaizumi, M.;Kadowaki, T.
目的/假设血浆脂联素水平的降低已被证明有助于糖尿病的发展。然而，脂联素是否在调节胰岛素分泌中起作用仍不确定。方法在体内外实验中观察脂联素对胰岛素分泌的影响，沿着脂联素对ATP生成、膜电位、钙电流、胞浆钙浓度和5 '-腺苷酸激活蛋白激酶（AMPK）状态的影响。此外，胰岛素颗粒运输测量膜电容和全内反射荧光（TIRF）analysis.Results脂联素显着刺激胰岛分泌胰岛素约2.3倍的基线值的存在下，葡萄糖浓度为5.6 mmol/l。虽然脂联素对ATP生成、膜电位、Ca 2+电流、胞浆钙浓度或AMPK活化状态没有影响，但它引起膜电容显著增加，约为基线值的2.3倍。TIRF分析显示，脂联素诱导小鼠胰腺β细胞在5.6 mmol/l葡萄糖负荷下融合事件的数量显著增加，而不影响先前停靠颗粒的状态。此外，静脉注射脂联素显着增加胰岛素分泌约1.6倍的基线在C57 BL/6 mice.Conclusions/Interpretation上述结果表明，脂联素诱导胰岛素分泌在体外和体内。
Aims/hypothesis A decrease in plasma adiponectin levels has been shown to contribute to the development of diabetes. However, it remains uncertain whether adiponectin plays a role in the regulation of insulin secretion. In this study, we investigated whether adiponectin may be involved in the regulation of insulin secretion in vivo and in vitro.Methods The effect of adiponectin on insulin secretion was measured in vitro and in vivo, along with the effects of adiponectin on ATP generation, membrane potentials, Ca2+ currents, cytosolic calcium concentration and state of 5 '-AMP-activated protein kinase (AMPK). In addition, insulin granule transport was measured by membrane capacitance and total internal reflection fluorescence (TIRF) analysis.Results Adiponectin significantly stimulated insulin secretion from pancreatic islets to approximately 2.3-fold the baseline value in the presence of a glucose concentration of 5.6 mmol/l. Although adiponectin had no effect on ATP generation, membrane potentials, Ca2+ currents, cytosolic calcium concentrations or activation status of AMPK, it caused a significant increase of membrane capacitance to approximately 2.3-fold the baseline value. TIRF analysis revealed that adiponectin induced a significant increase in the number of fusion events in mouse pancreatic beta cells under 5.6 mmol/l glucose loading, without affecting the status of previously docked granules. Moreover, intravenous injection of adiponectin significantly increased insulin secretion to approximately 1.6-fold of baseline in C57BL/6 mice.Conclusions/Interpretation The above results indicate that adiponectin induces insulin secretion in vitro and in vivo.