TYRAMINE EFFECTS ON GLUCAGON SECRETION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 1型糖尿病(T1D)患者患低血糖(低血糖)的风险很高，因为他们没有适当地分泌反调节激素胰高血糖素来应对低血糖。这种缺陷可能至少部分是由于从交感神经系统到胰腺的信号受损。1型糖尿病的动物模型在病程的早期就失去了刺激胰腺中产生胰高血糖素细胞的交感神经，这导致这些糖尿病动物无法在刺激支配胰腺的交感神经时释放胰高血糖素。据推测，这种神经缺陷可能是由于支配胰腺的神经受到自身免疫攻击所致，类似于导致1型糖尿病的过程，即免疫系统故障攻击胰腺中制造胰岛素的β细胞。 我们的目标是通过使用酪胺对胰腺进行交感神经刺激来证明健康受试者的胰升糖素反应，酪胺是一种导致交感神经递质直接局部释放的药物。利用这种药物，我们将尝试开发一种研究工具，以提高我们研究交感神经信号对胰高血糖素反应的能力。最终，这一工具将被用于研究1型糖尿病患者胰高血糖素反应异常的病因，这种缺陷会使他们面临严重低血糖以及随之而来的发病率和死亡率的风险。

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. Patients with type 1 diabetes (T1D) are at high risk for hypoglycemia (low blood sugars) because they do not secrete the counterregulatory hormone glucagon appropriately in response to hypoglycemia. This defect is probably due, at least in part, to an impaired signal from the sympathetic nervous system to the pancreas. Animal models of type 1 diabetes lose the sympathetic nerves that stimulate the glucagon-producing cells in the pancreas very early in their disease course, and this results in the inability of these diabetic animals to release glucagon in response to stimulation of the sympathetic nerves innervating the pancreas. It is hypothesized that this neurological defect may result from an autoimmune attack on the nerves innervating the pancreas, similar to the process that results in type 1 diabetes, in which a malfunctioning immune system attacks the beta cells of the pancreas that make insulin. Our aim is to demonstrate a glucagon response in healthy subjects via sympathetic stimulation of the pancreas using tyramine, a drug which causes the direct local release of sympathetic neurotransmitters. Using this drug, we will attempt to develop a research tool that will improve our ability to study the glucagon response to sympathetic nerve signals. Ultimately, this tool will be used to study the etiology of the abnormal glucagon response in patients with type 1 diabetes, a defect which puts them at risk for severe hypoglycemia and consequent morbidity and mortality.