Acosta-Martínez Maricedes, Levine Jon E
Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Dr., Evanston, IL 60208, USA.
Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1801-7. doi: 10.1152/ajpendo.00700.2006. Epub 2007 Feb 20.
The ATP-sensitive potassium (K(ATP)) channels are gated by intracellular adenine nucleotides coupling cell metabolism to membrane potential. Channels comprised of Kir6.2 and SUR1 subunits function in subpopulations of mediobasal hypothalamic (MBH) neurons as an essential component of a glucose-sensing mechanism in these cells, wherein uptake and metabolism of glucose leads to increase in intracellular ATP/ADP, closure of the channels, and increase in neuronal excitability. However, it is unknown whether glucose and/or insulin may also regulate the gene expression of the channel subunits in the brain. The present study investigated whether regulation of K(ATP) channel subunit gene expression might be a mechanism by which neuronal populations adapt to prolonged changes in glucose and/or insulin levels in the periphery. Ovariectomized, steroid-replaced rats were fitted with indwelling jugular catheters and infused for 48 h with saline, glucose (hyperglycemia-hyperinsulinemia), insulin and glucose (hyperinsulinemia), diazoxide (control), or glucose and diazoxide (hyperglycemia). At the end of infusions, the MBH, preoptic area, and pituitary were dissected for RNA isolation and RT-PCR. Hyperglycemia decreased Kir6.2 mRNA levels in the MBH in both the presence and absence of hyperinsulinemia. These same conditions also produced a trend toward decreased SUR1 mRNA levels in the MBH; however, it did not exceed statistical significance. Hyperglycemia increased whereas hyperinsulinemia reduced neuropeptide Y mRNA levels when these groups were compared with each other. However, neither was significantly different from values observed in saline-infused controls. In conclusion, hyperglycemia per se may alter expression of K(ATP) channels and thereby induce changes in the excitability of some MBH neurons.
ATP敏感性钾(K(ATP))通道受细胞内腺嘌呤核苷酸门控,将细胞代谢与膜电位相偶联。由Kir6.2和SUR1亚基组成的通道在下丘脑中部基底(MBH)神经元亚群中发挥作用,是这些细胞中葡萄糖感应机制的重要组成部分,其中葡萄糖的摄取和代谢导致细胞内ATP/ADP增加、通道关闭以及神经元兴奋性增加。然而,葡萄糖和/或胰岛素是否也能调节大脑中通道亚基的基因表达尚不清楚。本研究调查了K(ATP)通道亚基基因表达的调节是否可能是神经元群体适应外周葡萄糖和/或胰岛素水平长期变化的一种机制。切除卵巢并用类固醇替代的大鼠植入颈静脉导管,分别用生理盐水、葡萄糖(高血糖-高胰岛素血症)、胰岛素和葡萄糖(高胰岛素血症)、二氮嗪(对照)或葡萄糖和二氮嗪(高血糖)灌注48小时。灌注结束时,解剖MBH、视前区和垂体以分离RNA并进行逆转录聚合酶链反应(RT-PCR)。无论有无高胰岛素血症,高血糖均降低MBH中Kir6.2 mRNA水平。相同条件下,MBH中SUR1 mRNA水平也有降低趋势;然而,未超过统计学显著性。与其他组相比,高血糖使神经肽Y mRNA水平升高,而高胰岛素血症使其降低。然而,两者与生理盐水灌注对照组观察到的值均无显著差异。总之,高血糖本身可能改变K(ATP)通道的表达,从而诱导一些MBH神经元兴奋性的变化。