Aalinkeel R, Srinivasan M, Song F, Patel M S
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
Am J Physiol Endocrinol Metab. 2001 Sep;281(3):E640-8. doi: 10.1152/ajpendo.2001.281.3.E640.
To investigate the influence of a high carbohydrate (HC) intake during the suckling period on pancreatic function in adult life, neonatal rats were artificially reared on a HC milk formula during the preweaning period and then weaned onto lab chow. In the adult HC rat, hyperinsulinemia is sustained by a variety of biochemical and molecular adaptations induced in the HC islets during the suckling period. The adult HC islets showed a distinct left shift in the glucose-stimulated insulin-secretory pattern. HC islets were also able to secrete moderate levels of insulin in the absence of glucose and in the presence of Ca(2+) channel inhibitors. In addition, the mRNA levels of preproinsulin, somatostatin transcription factor-1, upstream stimulatory factor-1, stress-activated protein kinase-2, phosphatidylinositol kinase, and GLUT-2 genes were significantly increased in HC islets. These results show that consumption of a HC formula during the suckling period programs pancreatic islet function in adult rats, resulting in the maintenance of hyperinsulinemia in the postweaning period and eventually leading to the development of obesity in adult life.
为了研究哺乳期高碳水化合物(HC)摄入对成年期胰腺功能的影响,新生大鼠在断奶前阶段用HC奶粉人工饲养,然后断奶并给予实验室饲料。在成年HC大鼠中,哺乳期HC胰岛中诱导的各种生化和分子适应性变化维持了高胰岛素血症。成年HC胰岛在葡萄糖刺激的胰岛素分泌模式上出现明显的左移。HC胰岛在无葡萄糖和存在Ca(2+)通道抑制剂的情况下也能够分泌中等水平的胰岛素。此外,HC胰岛中胰岛素原、生长抑素转录因子-1、上游刺激因子-1、应激激活蛋白激酶-2、磷脂酰肌醇激酶和GLUT-2基因的mRNA水平显著升高。这些结果表明,哺乳期食用HC配方奶粉可对成年大鼠胰岛功能进行编程,导致断奶后高胰岛素血症的维持,并最终导致成年期肥胖的发生。