title: Early sympathetic islet neuropathy in autoimmune diabetes: lessons learned and opportunities for investigation.
abstract: This review outlines the current state of knowledge regarding a unique neural defect of the pancreatic islet in autoimmune diabetes, one that we have termed early sympathetic islet neuropathy (eSIN). We begin with the findings that a majority of islet sympathetic nerves are lost near the onset of type 1, but not type 2, diabetes and that this nerve loss is restricted to the islet. We discuss later work demonstrating that while the loss of islet sympathetic nerves and the loss of islet beta cells in type 1 diabetes both require infiltration of the islet by lymphocytes, their respective mechanisms of tissue destruction differ. Uniquely, eSIN requires the activation of a specific neurotrophin receptor and we propose two possible pathways for activation of this receptor during the immune attack on the islet. We also outline what is known about the functional consequences of eSIN, focusing on impairment of sympathetically mediated glucagon secretion and its application to the clinical problem of insulin-induced hypoglycaemia. Finally, we offer our view on the important remaining questions regarding this unique neural defect.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, 98105, USA. mundin@u.washington.edu.|Veterans Affairs Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA, 98108, USA. mundin@u.washington.edu.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Mundinger
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, 98105, USA.|Veterans Affairs Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA, 98108, USA.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Taborsky
mesh_terms: D015551:Autoimmunity / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*
chemical_list: D009414:Nerve Growth Factors; D005934:Glucagon
keywords: Autoimmunity; Diabetes; Glucagon; Human; Insulin-induced hypoglycaemia; Islet; Neuropathy; Neurotrophins; Review; Rodent; Sympathetic nerves