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
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