日本自治醫(yī)科大學(xué)教授矢田俊彥率領(lǐng)的研究小組日前宣布，他們發(fā)現(xiàn)了人體進(jìn)食后部分物質(zhì)如何使大腦產(chǎn)生吃飽的感覺,。進(jìn)一步的研究有望讓研究人員開發(fā)出新療法治療暴食和肥胖等病癥,。
此前的研究已發(fā)現(xiàn),，人體進(jìn)食時(shí)，在作為食欲中樞的丘腦下部室旁核中,，一種稱為“nesfatin-1”的蛋白質(zhì)會(huì)增加,，讓人產(chǎn)生吃飽感。但具體機(jī)制如何運(yùn)作一直是個(gè)謎,。
研究人員在小鼠身上進(jìn)行實(shí)驗(yàn)來探究這一機(jī)制,，他們從小鼠的室旁核中取出腦神經(jīng)細(xì)胞，標(biāo)定了一些含有“nesfatin-1”蛋白質(zhì)的細(xì)胞,，并發(fā)現(xiàn)這種細(xì)胞能與高濃度的葡萄糖和胰島素發(fā)生反應(yīng)并被激活,。由于人們進(jìn)食米飯和面包等碳水化合物后，血液中的葡萄糖和胰島素的濃度會(huì)增加,，因此上述的反應(yīng)可能是大腦產(chǎn)生吃飽感的部分原因,。
研究小組3月24日在線發(fā)表于《生物化學(xué)和生物物理研究通訊》（Biochemical and Biophysical Research Communications）上的論文指出，如果今后能弄清蛋白質(zhì)的氨基酸和類脂化合物對吃飽感有何影響,，以及進(jìn)食時(shí)間不同導(dǎo)致的吃飽感差異,，就有望開發(fā)出新療法對暴食、肥胖等病癥進(jìn)行有效治療,。（生物谷 bioon.com）
doi:10.1016/j.bbrc.2012.03.079
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Glucose and insulin induce Ca2+ signaling in nesfatin-1 neurons in the hypothalamic paraventricular nucleus
Darambazar Gantulga, , Yuko Maejima, , Masanori Nakata, , Toshihiko Yada
Nucleobindin-2 derived nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) plays a role in inhibition of feeding. The neural pathways downstream of PVN nesfatin-1 have been extensively investigated. However, regulation of the PVN nesfatin-1 neurons remains unclear. Since starvation decreases and refeeding stimulates nesfatin-1 expression specifically in the PVN, this study aimed to clarify direct effects of meal-evoked metabolic factors, glucose and insulin, on PVN nesfatin-1 neurons. High glucose (10 mM) and insulin (10?13 M) increased cytosolic calcium concentration ([Ca2+]i) in 55 of 331 (16.6%) and 32 of 249 (12.9%) PVN neurons, respectively. Post [Ca2+]i measurement immunocytochemistry identified that 58.2% of glucose-responsive and 62.5% of insulin-responsive neurons were immunoreactive to nesfatin-1. Furthermore, a fraction of the glucose-responsive nesfatin-1 neurons also responded to insulin, and vice versa. Some of the neurons that responded to neither glucose nor insulin were recruited to [Ca2+]i increases by glucose and insulin in combination. Our data demonstrate that glucose and insulin directly interact with and increase [Ca2+]i in nesfatin-1 neurons in the PVN, and that the nesfatin-1 neuron is the primary target for them in the PVN. The results suggest that high glucose- and insulin-induced activation of PVN nesfatin-1 neurons serves as a mechanism through which meal ingestion stimulates nesfatin-1 neurons in the PVN and thereby produces satiety.
