METABOLIC EPINEPHRINE SENSITIVITY IN DIABETES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在1型糖尿病患者中，肾上腺素反应在低血糖恢复中起着至关重要的作用。肾上腺素通过增加胰岛素抵抗、增加脂肪分解和增加葡萄糖生成来促进低血糖的恢复。最近的几项研究表明，低血糖患者和既往低血糖患者的心脏β-肾上腺素能敏感性发生改变。这些研究还没有探索肾上腺素的代谢敏感性。这项研究的目标是确定糖尿病控制和先期低血糖如何影响肾上腺素诱导的胰岛素抵抗、脂肪分解和内源性葡萄糖产生。为此，我们将研究14名健康受试者和14名糖尿病控制和控制不良的受试者。每个受试者将进行两次研究，一次是先患正常血糖，一次是先患低血糖。肾上腺素诱导的胰岛素抵抗将通过正糖高胰岛素葡萄糖钳夹注射肾上腺素期间的动静脉血糖差和前臂血流量测定前臂葡萄糖摄取量来测量。脂肪分解和内源性葡萄糖的产生将分别用稳定标记的甘油和葡萄糖来测量。低血糖是强化糖尿病治疗在实现良好的血糖控制和预防糖尿病并发症方面的限速性副作用。建议的研究将帮助我们更多地了解身体如何保护自己免受低血糖和1型糖尿病潜在异常的影响。

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. In type 1 diabetic patients the epinephrine response plays a crucial role in hypoglycemic recovery. Epinephrine promotes hypoglycemic recovery by increasing insulin resistance, increasing lipolysis, and increasing glucose production. Several recent studies have demonstrated that cardiac beta-adrenergic sensitivity is altered in patients with hypoglycemia and by antecedent hypoglycemia. These studies have not explored metabolic sensitivity to epinephrine. The goals of this study are to determine how diabetes control and antecedent hypoglycemia affect epinephrine-induced insulin resistance, lipolysis, endogenous glucose production. To do this we will study 14 healthy subjects and 14 subjects with controlled and poorly controlled diabetes. Each subject will be studied twice, once with antecedent euglycemia and once with antecedent hypoglycemia. Epinephrine-induced insulin resistance will be measured through forearm glucose uptake determined from arterial-venous glucose difference and forearm blood flow during euglycemic hyperinsulinemic glucose clamp with epinephrine infusion. Lipolysis and endogenous glucose production will be measured by using stable labeled glycerol and glucose, respectively. Hypoglycemia is the rate limiting side effect of intensive diabetes therapy in achieving good glucose control and prevention of diabetic complications. The studies proposed will help us learn more about how the body protects itself from hypoglycemia and potential abnormalities in type 1 diabetes