DIET INDUCED HYPERINSULINEMIA AND BETA CELL FUNCTION

描述：喂食高碳水化合物(HC)奶粉的新生大鼠使用 一种哺乳期间的人工饲养系统 胰腺胰岛素含量和分泌活性的变化 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之外，只有 成年大鼠。此外，HC大鼠的后代表现为HI，并改变了血糖 晚年的耐受性和肥胖症。该项目的目标是 调查导致早期适应性修改的机制 胰岛细胞对HC饮食和代谢的反应 HI大鼠胚胎胰腺的适应性。三个具体目标是：(1) 探讨胰岛素分泌改变的机制(S) 第一代HC大鼠的胰岛反应。无血浆 脂肪酸和甘油三酯水平将在发育过程中进行测定 嗨。假设是在生命早期喂食高碳水化合物的饮食 影响修饰胰岛素的胰岛β细胞的燃料代谢 分泌物，并在成年生活中持续存在。(二)调查影响 母体缺氧对婴儿胰岛素分泌反应改变的影响 后代出生后的生活。(3)测定特定酶的活性 新生儿期、幼年期和幼年期胰岛的第二信使系统 用母乳喂养的成年大鼠(MF大鼠)或富含脂肪的饮食 (HF大鼠)或碳水化合物(HC大鼠)。假设是连续的 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、腺苷环化酶及其酶/蛋白 它们有助于磷脂酰肌醇途径的功能和 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 对饮食的反应和母亲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.