TYRAMINE EFFECTS ON GLUCAGON SECRETION

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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