Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice.
Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice.
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作者：
Coomans CP;Biermasz NR;Geerling JJ;Guigas B;Rensen PC;Havekes LM;Romijn JA
胰岛素抑制内源性葡萄糖的产生(EGP)并刺激外周组织对葡萄糖的摄取。胰岛素对EGP的抑制作用需要下丘脑胰岛素信号转导。我们研究了中枢胰岛素信号在循环胰岛素刺激的组织特异性葡萄糖摄取中的作用。将三磷酸腺苷敏感钾通道(KATP通道)的抑制剂甲苯丁胺或赋形剂注入基础状态和高胰岛素-正常血糖状态下的C57BL/6J小鼠和饮食诱导肥胖的吸收后C57BL/6J小鼠。通过d-[14C]葡萄糖动力学和2-脱氧-d-[~3H]葡萄糖摄取测量组织特异性葡萄糖摄取。在钳制条件下，侧脑室注射甲苯丁胺可削弱胰岛素抑制∼20%的能力。此外，脑室注射甲苯丁胺可减少肌肉中胰岛素刺激的葡萄糖摄取(∼为59%)，但心脏或脂肪组织中的摄取不受影响。相比之下，在饮食诱导肥胖的胰岛素抵抗小鼠中，脑室内注射甲苯丁胺并不改变夹闭条件下胰岛素对EGP或肌肉摄取葡萄糖的影响。胰岛素刺激肌肉中葡萄糖摄取的部分作用是通过中枢神经系统中的KATP通道，类似于胰岛素对EGP的抑制作用。高脂饮食导致的肥胖消除了胰岛素对肝脏和肌肉的中枢作用。这些观察强调了中枢胰岛素抵抗在饮食诱导的胰岛素抵抗的病理生理学中的作用。
Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin–stimulated tissue-specific glucose uptake. Tolbutamide, an inhibitor of ATP-sensitive K+ channels (KATP channels), or vehicle was infused into the lateral ventricle in the basal state and during hyperinsulinemic-euglycemic conditions in postabsorptive, chow-fed C57Bl/6J mice and in postabsorptive C57Bl/6J mice with diet-induced obesity. Whole-body glucose uptake was measured by d-[14C]glucose kinetics and tissue-specific glucose uptake by 2-deoxy-d-[3H]glucose uptake. During clamp conditions, intracerebroventricular administration of tolbutamide impaired the ability of insulin to inhibit EGP by ∼20%. In addition, intracerebroventricular tolbutamide diminished insulin-stimulated glucose uptake in muscle (by ∼59%) but not in heart or adipose tissue. In contrast, in insulin-resistant mice with diet-induced obesity, intracerebroventricular tolbutamide did not alter the effects of insulin during clamp conditions on EGP or glucose uptake by muscle. Insulin stimulates glucose uptake in muscle in part through effects via KATP channels in the central nervous system, in analogy with the inhibitory effects of insulin on EGP. High-fat diet–induced obesity abolished the central effects of insulin on liver and muscle. These observations stress the role of central insulin resistance in the pathophysiology of diet-induced insulin resistance.
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影响因子：
--
作者：
ARASE, K;FISLER, JS;BRAY, GA
通讯作者：
BRAY, GA
影响因子：
7.7
作者：
Toda C;Shiuchi T;Lee S;Yamato-Esaki M;Fujino Y;Suzuki A;Okamoto S;Minokoshi Y
通讯作者：
Minokoshi Y
影响因子：
3.2
作者：
van den Hoek, A. M.;Teusink, B.;Pijl, H.
通讯作者：
Pijl, H.
影响因子：
7.7
作者：
HOLLENBECK, CB;CHEN, YDI;REAVEN, GM
通讯作者：
REAVEN, GM
影响因子：
6.5
作者：
Heijboer, AC;Donga, E;Corssmit, EPM
通讯作者：
Corssmit, EPM