GLUCOSE TRANSPORT REGULATION IN SMALL INTESTINE

高亲和力Na+/葡萄糖的肠道表达 协同转运蛋白（SGLT 1），负责吸收 饮食葡萄糖和半乳糖，表现出昼夜节律周期性， 其活性和由膳食碳水化合物诱导。 因为日常 SGLT 1活性的变化由饲喂时间表确定 （无论是随意或强制），并坚持在没有食物， 这种变化被描述为预期性的。 我们提供 有证据表明这种预期节奏的遗传基础。 的 在大鼠中检查了SGLT 1表达的正常日周期性 维持在12小时光周期中，并允许自由进食。 SGLT 1 mRNA水平变化高达10倍，最大丰度为 在光周期的暗相开始附近发生， 最小值接近光的开始。 SGLT 1转录也 变化，与密度估计率（相对于 - 微管蛋白）6.4 q在1000 h和1100 h之间比 在1600 h和1700 h之间（n=4; p<.007，双尾t检验）。 我们克隆 大鼠SGLT 1近端启动子区，并确定了一个元件， 肝细胞核因子1（HNF-1）在大鼠和人之间是保守的。 由该元素产生的探针与 小肠核提取物，取决于当源动物 被杀了 血清学试验表明，HNF-1a存在于 所有复合物，而HNF-1b在1600 h和2200 h时存在，但在2200 h时不存在。 在0400时或1000时。我们认为HNF-1二聚化的交换 伴侣有助于SGLT 1转录的昼夜变化。 HNF-1的这种扩大的作用暗示了这种同源异型蛋白在颞叶神经元中的作用。 模式的形成除了它在空间模式中的典型作用之外 阵 因为我们也观察到了不同的SGLT 1 mRNA， 恒河猴体内的浓度水平（从 大鼠），我们认为在灵长类动物中存在类似的机制。 这项研究已被接受出版的杂志 生物化学. 目前正在等待一笔用于延长这些研究的一级拨款 （NIDDK）.

Intestinal expression of the high-affinity Na+/glucose cotransporter (SGLT1), which is responsible for the absorption of dietary glucose and galactose, exhibits both circadian periodicity in its activity and induction by dietary carbohydrate. Because the daily variation in SGLT1 activity is established by the feeding schedule (whether ad libitum or imposed) and persists in the absence of food, this variation has been described as anticipatory. We provide evidence indicating a genetic basis for this anticipatory rhythm. The normal daily periodicity in SGLT1 expression has been examined in rats maintained in a 12-h photoperiod and allowed free access to chow. SGLT1 mRNA levels varied up to 10-fold, with the maximum abundance occurring near the beginning of the dark phase of the photoperiod and the minimum near the onset of light. SGLT1 transcription also changes, with the rate estimated densitometrically (relative to -tubulin) 6.4 q 1.0 times greater between 1000 h and 1100 h than between 1600 h and 1700 h (n=4; p<.007, 2-tailed t-Test). We cloned the rat SGLT1 proximal promoter region and identified an element for hepatocyte nuclear factor 1 (HNF-1) conserved between rat and human. A probe generated from this element formed different complexes with small intestinal nuclear extracts, depending on when the source animal was killed. Serological tests indicated that HNF-1a was present in all complexes, while HNF-1b was present at 1600 h and 2200 h but not at 0400 h or 1000 h. We propose that exchange of HNF-1 dimerization partners contributes to circadian changes in SGLT1 transcription. This expanded role for HNF-1 implicates this homeoprotein in temporal pattern formation in addition to its canonical role in spatial pattern formation. because we have also observed differential SGLT1 mRNA levels in rhesus monkeys (off-set by approximately one-half day from rats), we suggest that a similar mechanism is present in primates. This study has been accepted for publication by the Journal of Biological Chemistry. An RO1 grant is pending to extend these studies (NIDDK).