The p75 Neurotrophin Receptor Is Required for the Major Loss of Sympathetic Nerves From Islets Under Autoimmune Attack
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چکیده
Our goal was to determine the role of the p75 neurotrophin receptor (p75NTR) in the loss of islet sympathetic nerves that occurs during the autoimmune attack of the islet. The islets of transgenic (Tg) mice in which β-cells express a viral glycoprotein (GP) under the control of the insulin promotor (Ins2) were stained for neuropeptide Y before, during, and after virally induced autoimmune attack of the islet. Ins2-GP(Tg) mice injected with lymphocytic choriomeningitis virus (LCMV) lost islet sympathetic nerves before diabetes development but coincident with the lymphocytic infiltration of the islet. The nerve loss was marked and islet-selective. Similar nerve loss, chemically induced, was sufficient to impair sympathetically mediated glucagon secretion. In contrast, LCMV-injected Ins2-GP(Tg) mice lacking the p75NTR retained most of their islet sympathetic nerves, despite both lymphocytic infiltration and development of diabetes indistinguishable from that of p75NTR wild-type mice. We conclude that an inducible autoimmune attack of the islet causes a marked and islet-selective loss of sympathetic nerves that precedes islet collapse and hyperglycemia. The p75NTR mediates this nerve loss but plays no role in mediating the loss of islet β-cells or the subsequent diabetes. p75NTR-mediated nerve loss may contribute to the impaired glucose counterregulation seen in type 1 diabetes.
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