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首页> 外文学位 >Central leptin administration increases insulin sensitivity, independent of food intake, and sympathetic activity in diabetic rats.
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Central leptin administration increases insulin sensitivity, independent of food intake, and sympathetic activity in diabetic rats.

机译：在糖尿病大鼠中，中央瘦素​​给药可增加胰岛素敏感性，而与食物摄入量和交感活动无关。

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摘要

Leptin, an adipocyte-derived hormone, has been associated with both obesity and diabetes. Previous studies have suggested that leptin may play an important role in overall energy metabolism, especially with regard to glucose metabolism. To further address this issue, we examined the effects of central leptin on insulin sensitivity in diabetic rats. Animals were implanted with an intracebroventricular (ICV) cannula directed to the lateral ventricle. Streptozotocin (50 mg/kg I.V.) was administered to induce diabetes. Chronic daily injections of ICV leptin (10 μg/day) or vehicle were given beginning 2 days after the establishment of hyperglycemia in diabetic animals. To determine the effect of leptin independent of changes in food intake, pair-feeding was performed by assigning each pair-fed rat to a partner in the leptin treatment group. The amount of food provided to each pair-fed animal on each treatment day was equal to the measured amount consumed by its leptin-treated partner during the previous 24-hour period. At the completion of the study, rats were fasted for six hours, and insulin sensitivity was evaluated by the steady-state plasma glucose (SSPG) method. A jugular cannula was used to continuously infuse insulin (2.5 mU/kg/min), glucose (8 mg/kg/min), and somatostatin (0.5 μg/min) for 170 min. SSPG was determined during the last 20 minutes of infusion. By the third day of central leptin injection, blood glucose concentrations dramatically decreased in diabetic animals and were normalized by the fourth day. This level was maintained throughout the remainder of the study. While diabetic rats were insulin resistant, insulin sensitivity was dramatically increased in leptin-treated animals. Body weight of leptin-treated rats was not decreased. Food restriction did not normalize blood glucose concentrations in diabetic rats. Therefore, the effect of leptin was independent of food intake and body weight. Plasma catecholamine concentrations were significantly increased, suggesting sympathetic activation after central leptin administration. Circulating leptin levels were not increased in animals injected with central leptin. Thus, it appears that central leptin leads to an increase in the sensitivity to circulating insulin, which helps to normalize blood glucose concentrations in diabetic animals. Conversely, these data are consistent with the idea that low central leptin status, whether caused by low circulating leptin levels or leptin resistance, may lead to insulin resistance.
机译：瘦素是一种来自脂肪细胞的激素，与肥胖和糖尿病都有关系。先前的研究表明，瘦素可能在整体能量代谢中起重要作用，尤其是在葡萄糖代谢方面。为了进一步解决这个问题，我们研究了中央瘦素对糖尿病大鼠胰岛素敏感性的影响。动物植入了指向侧脑室的脑室内（ICV）套管。施用链脲佐菌素（50mg / kg静脉内）以诱发糖尿病。在糖尿病动物高血糖症建立后的第二天开始，每天慢性注射ICV瘦蛋白（10μg/天）或赋形剂。为了确定瘦素的效果与食物摄入量的变化无关，通过将每对成对喂养的大鼠分配给瘦素治疗组中的伴侣来进行成对喂养。在每个治疗日提供给每对配对动物的食物量等于其前24小时内经瘦素治疗的伴侣所测得的食物量。在研究完成时，大鼠禁食六个小时，并通过稳态血浆葡萄糖（SSPG）方法评估胰岛素敏感性。使用颈静脉插管连续输注胰岛素（2.5 mU / kg / min），葡萄糖（8 mg / kg / min）和生​​长抑素（0.5μg/ min）170分钟。在输注的最后20分钟内确定SSPG。到中央瘦素注射的第三天，糖尿病动物的血糖浓度急剧下降，并在第四天恢复正常。在其余的研究中，该水平一直保持。虽然糖尿病大鼠具有胰岛素抵抗性，但在用瘦素治疗的动物中胰岛素敏感性显着提高。瘦素治疗的大鼠的体重没有降低。食物限制不能使糖尿病大鼠的血糖浓度正常化。因此，瘦素的作用与食物摄入量和体重无关。血浆儿茶酚胺浓度显着增加，表明中央瘦素给药后交感神经激活。在注射中央瘦素的动物中，循环瘦素水平没有增加。因此，看来中央瘦素导致对循环胰岛素的敏感性增加，这有助于使糖尿病动物中的血糖浓度正常化。相反，这些数据与低中央瘦素状态（无论是低循环的瘦素水平还是瘦素抗性引起）可能导致胰岛素抵抗的想法是一致的。

著录项

  • 作者

    Lin, Chia-yu.;

  • 作者单位

    Auburn University.;

  • 授予单位 Auburn University.;
  • 学科 Health Sciences Nutrition.; Health Sciences Pathology.; Biology Animal Physiology.
  • 学位 Ph.D.
  • 年度 2002
  • 页码 143 p.
  • 总页数 143
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 预防医学、卫生学;病理学;生理学;
  • 关键词

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