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The search for the mechanism of early sympathetic islet neuropathy in autoimmune diabetes
Author(s) -
Taborsky G. J.,
Mei Q.,
Hackney D. J.,
Mundinger T. O.
Publication year - 2014
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12341
Subject(s) - islet , medicine , diabetes mellitus , glucagon , endocrinology , immune system , type 1 diabetes , sympathetic nervous system , insulin , immunology , blood pressure
This review outlines our search for the mechanism causing the early loss of islet sympathetic nerves in autoimmune diabetes. Since our previous work has documented the importance of autonomic stimulation of glucagon secretion during hypoglycaemia, the loss of these nerves may contribute to the known impairment of this specific glucagon response early in human type 1 diabetes. We therefore briefly review the contribution that autonomic activation, and sympathetic neural activation in particular, makes to the subsequent glucagon response to hypoglycaemia. We also detail evidence that animal models of autoimmune diabetes mimic both the early loss of islet sympathetic nerves and the impaired glucagon response seen in human type 1 diabetes. Using data from these animal models, we examine mechanisms by which this loss of islet nerves could occur. We provide evidence that it is not due to diabetic hyperglycaemia, but is related to the lymphocytic infiltration of the islet. Ablating the p75 neurotrophin receptor, which is present on sympathetic axons, prevents early sympathetic islet neuropathy (eSIN), but, interestingly, not diabetes. Thus, we appear to have separated the immune‐related loss of islet sympathetic nerves from the immune‐mediated destruction of islet β ‐cells. Finally, we speculate on a way to restore the sympathetic innervation of the islet.