TYRAMINE EFFECTS ON GLUCAGON SECRETION

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。1型糖尿病（T1D）患者发生低血糖（低血糖）的风险很高，因为他们在低血糖时不能适当地分泌反调节激素胰高血糖素。这种缺陷可能是由于，至少部分是由于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疾病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释放胰高血糖素，以响应支配胰腺的交感神经的刺激。据推测，这种神经缺陷可能是由支配胰腺的神经受到自身免疫攻击造成的，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。我们的目的是通过使用酪胺（一种直接局部释放交感神经递质的药物）刺激胰腺，在健康受试者中证明胰高血糖素的反应。使用这种药物，我们将尝试开发一种研究工具，以提高我们研究胰高血糖素对交感神经信号的反应的能力。最终，该工具将用于研究1型糖尿病患者胰高血糖素异常反应的病因，这一缺陷使他们面临严重低血糖和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