DIET INDUCED HYPERINSULINEMIA AND BETA CELL FUNCTION

描述：新生大鼠喂食高碳水化合物（HC）牛奶配方， 哺乳期人工饲养系统 胰岛素含量和胰腺分泌活性的改变 β细胞 新生儿高胰岛素血症（HI）是一种持续存在的后果 在成年生活中，除了糖耐量受损和肥胖外， 成年大鼠 此外，HC大鼠的后代显示HI和改变的葡萄糖 在以后的生活中的耐受性和肥胖。 该项目的目标是 研究负责早期适应性修改的机制， 胰岛细胞对HC饮食的反应以及代谢 HI大鼠胚胎胰腺的适应性变化。 三个具体目标是：（1） 研究胰岛素分泌改变的机制 第一代HC大鼠胰岛中的反应。 血浆游离 脂肪酸和甘油三酸酯水平将在开发过程中确定 嗨 这一假设是，在生命早期喂养的高碳水化合物饮食 影响胰腺β细胞的燃料代谢，从而改变胰岛素 分泌，并持续到成年。 (2)调查的影响 母体HI对胰岛素分泌反应改变的影响 后代出生后的生活。 (3)确定特定的活性 第二信使系统在来自新生儿、幼年和 用母乳（MF大鼠）或富含脂肪的饮食饲养的成年大鼠 (HF大鼠）或碳水化合物（HC大鼠）。 假设持续 早期的葡萄糖刺激改变了葡萄糖转运蛋白（GLUT-2）， 葡萄糖代谢酶、腺苷酸环化酶和酶/蛋白质 其有助于磷酸肌醇途径的功能， β细胞以正常方式调节胰岛素分泌的能力。 这种独特的大鼠模型有可能提供新的和重要的 对胰岛素分泌反应改变的“燃料假说”的认识 对饮食的反应和母体对胎儿胰腺适应的影响。

DESCRIPTION: Neonatal rats fed a high-carbohydrate (HC) milk formula using an artificial rearing system during the suckling period experience alterations in the insulin content and secretory activity of the pancreatic beta cells. Neonatal hyperinsulinemia (HI) is a consequence which persists in adult life, in addition to impaired glucose tolerance and obesity only in adult rats. In addition, progeny of HC rats display HI, and altered glucose tolerance and obesity in later life. The goals of this project are to investigate the mechanisms responsible for early adaptive modifications in pancreatic islet cells in response to a HC diet and also metabolic adaptations in fetal pancreas of HI rats. Three specific aims are to: (1) To investigate the mechanism(s) responsible for altered insulin secretory response in pancreatic islets from first generation HC rats. Plasma free fatty acid and triglyceride levels will be determined during development of HI. The hypothesis is that a high carbohydrate diet fed early in life affects fuel metabolism in the pancreatic beta cell which modifies insulin secretion and persists in adult life. (2) Investigate the influence of maternal HI on the development of an altered insulin secretory response in the postnatal life of offspring. (3) Determine the activity of specific second messenger systems in islets derived from neonatal, junvenile and adult rats reared on mother's milk (MF rats) or on a diet enriched in fat (HF rats) or carbohydrate (HC rats). The hypothesis is that continuous glucose stimulation at an early age alters the glucose transporter (GLUT-2), glucose metabolizing enzymes, adenylate cyclase and the enzymes/proteins which contribute to the functioning of the phosphoinositide pathway and the ability of the beta cell to regulate insulin secretion in a normal fashion. This unique rat model has the potential for providing new and significant insight into the "fuel hypothesis" for altered insulin secretory response in response to diet and maternal influences on fetal pancreatic adaptations.