GLUCOSE EXCURSIONS: ROLE OF AMYLIN AND GLUCAGON

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。糖尿病控制和并发症试验（DCCT）表明，大多数T1DM患者应接受强化治疗，以降低并发症的风险。在年幼的糖尿病患儿中，严格的糖尿病控制是以不可接受的高低血糖发生率为代价的。T1DM被认为是一种双激素疾病，其中胰岛素缺乏和胰高血糖素失调导致餐后高血糖和餐前低血糖。除了胰高血糖素，我们现在正在了解其他可能导致糖尿病激素生成障碍的激素。其中一种激素是胰淀素。胰淀素由细胞分泌，是一种独特的胰高血糖素抑制因子。胰淀素缺乏和胰高血糖素失调可导致T1DM中常见的异常葡萄糖漂移。尽管使用了较新的胰岛素类似物和胰岛素泵，但目前的T1DM治疗采用胰岛素药代动力学和饮食控制来使葡萄糖漂移正常化，但效果有限。该建议旨在使用一种新的双管齐下的方法，使用普兰林肽，一种合成形式的胰高血糖素来对抗餐后高血糖和注射胰高血糖素来预防餐前低血糖。本研究将首次探讨胰高血糖素和胰高血糖素在预防小儿T1DM患者高血糖和低血糖中的药物治疗作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Diabetes Control and Complications Trial (DCCT) demonstrated that most patients with T1DM should receive intensive treatment to lower the risks of complications. In younger children with diabetes, strict diabetes control is achieved at the expense of unacceptably high incidence of hypoglycemia. T1DM is considered a bihormonal disease wherein there is insulin deficiency and glucagon dysregulation resulting in post-prandial hyperglycemia and pre-prandial hypoglycemia. In addition to glucagon we are now learning of other hormones that may contribute to the dyshormonogenesis of diabetes. One such hormone is amylin. Amylin is secreted by beta cells and is an exclusive glucagon suppressor. Amylin deficiency and glucagon dysregulation in T1DM may result in abnormal glucose excursions often seen in T1DM. Current treatment of T1DM employs the manipulation of insulin pharmacokinetics and diet to normalize glucose excursions with limited success despite the use of newer insulin analogs and insulin pumps. This proposal aims at using a novel two pronged approach using pramlintide, a synthetic form of amylin to combat post-prandial hyperglycemia and glucagon injection to prevent pre-prandial hypoglycemia. This study for the first time will investigate the pharmacotherapeutic role of amylin and glucagon in the prevention of hyper and hypoglycemia in pediatric T1DM.