Mithieux Gilles
Inserm 855, UCBLyon 1.
Bull Acad Natl Med. 2007 Apr-May;191(4-5):911-20; discussion 920-1.
The interactions between glucose and energy homeostasis are well known. In particular, a high portal vein glucose concentration suppresses food intake. Numerous studies point to a glucose-sensing mechanism involving nerves present in the wall of the portal vein. We have studied the expression of genes involved in gluconeogenesis in the rat and human intestine, in terms of mRNA and protein levels and enzyme activity. Intestinal glucose production was quantified by using a combination of (3-3H) glucose tracer dilution and arterio-venous glucose balance. The effect of the portal glucose level on food intake was studied in conscious rats with indwelling portal vein catheters. The hypothalamic consequences of glucose infusion were studied by c-Fos protein immunodetection. All regulatory genes involved in gluconeogenesis were strongly induced by fasting and by a protein-rich diet. In both cases the glucose level in the portal vein increased, an effect that lasted some time after a protein-rich meal. Glucose infusion into the portal vein led to a decrease in food intake and activated hypothalamic regions involved in controlling food intake, in the same way as the protein-rich diet. The effects of portal glucose infusion and of the protein-rich diet were suppressed by inactivating the portal nervous system. These results provide a mechanistic explanation for the effect of satiety induced by a high-protein diet.
葡萄糖与能量稳态之间的相互作用已为人熟知。特别是,门静脉葡萄糖浓度升高会抑制食物摄入。众多研究指向一种涉及门静脉壁神经的葡萄糖感知机制。我们已经从mRNA和蛋白质水平以及酶活性方面研究了大鼠和人类肠道中参与糖异生的基因表达。通过使用(3-3H)葡萄糖示踪剂稀释和动静脉葡萄糖平衡相结合的方法对肠道葡萄糖生成进行了定量。在留置门静脉导管的清醒大鼠中研究了门静脉葡萄糖水平对食物摄入的影响。通过c-Fos蛋白免疫检测研究了葡萄糖输注对下丘脑的影响。所有参与糖异生的调节基因在禁食和富含蛋白质的饮食情况下均被强烈诱导。在这两种情况下,门静脉中的葡萄糖水平都会升高,富含蛋白质的餐后这种影响会持续一段时间。向门静脉输注葡萄糖会导致食物摄入减少,并激活参与控制食物摄入的下丘脑区域,这与富含蛋白质的饮食作用方式相同。通过使门静脉神经系统失活,门静脉葡萄糖输注和富含蛋白质饮食的作用均受到抑制。这些结果为高蛋白饮食诱导饱腹感的作用提供了一种机制解释。