Cargando…

Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves

In humans, the glucagon response to moderate-to-marked insulin-induced hypoglycemia (IIH) is largely mediated by the autonomic nervous system. Because this glucagon response is impaired early in type 1 diabetes, we sought to determine if these patients, like animal models of autoimmune diabetes, hav...

Descripción completa

Detalles Bibliográficos
Autores principales: Mundinger, Thomas O., Mei, Qi, Foulis, Alan K., Fligner, Corinne L., Hull, Rebecca L., Taborsky, Gerald J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955989/
https://www.ncbi.nlm.nih.gov/pubmed/27207540
http://dx.doi.org/10.2337/db16-0284
_version_ 1782443965273866240
author Mundinger, Thomas O.
Mei, Qi
Foulis, Alan K.
Fligner, Corinne L.
Hull, Rebecca L.
Taborsky, Gerald J.
author_facet Mundinger, Thomas O.
Mei, Qi
Foulis, Alan K.
Fligner, Corinne L.
Hull, Rebecca L.
Taborsky, Gerald J.
author_sort Mundinger, Thomas O.
collection PubMed
description In humans, the glucagon response to moderate-to-marked insulin-induced hypoglycemia (IIH) is largely mediated by the autonomic nervous system. Because this glucagon response is impaired early in type 1 diabetes, we sought to determine if these patients, like animal models of autoimmune diabetes, have an early and severe loss of islet sympathetic nerves. We also tested whether this nerve loss is a permanent feature of type 1 diabetes, is islet-selective, and is not seen in type 2 diabetes. To do so, we quantified pancreatic islet and exocrine sympathetic nerve fiber area from autopsy samples of patients with type 1 or 2 diabetes and control subjects without diabetes. Our central finding is that patients with either very recent onset (<2 weeks) or long duration (>10 years) of type 1 diabetes have a severe loss of islet sympathetic nerves (Δ = −88% and Δ = −79%, respectively). In contrast, patients with type 2 diabetes lose no islet sympathetic nerves. There is no loss of exocrine sympathetic nerves in either type 1 or type 2 diabetes. We conclude that patients with type 1, but not type 2, diabetes have an early, marked, sustained, and islet-selective loss of sympathetic nerves, one that may impair their glucagon response to IIH.
format Online
Article
Text
id pubmed-4955989
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-49559892017-08-01 Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves Mundinger, Thomas O. Mei, Qi Foulis, Alan K. Fligner, Corinne L. Hull, Rebecca L. Taborsky, Gerald J. Diabetes Islet Studies In humans, the glucagon response to moderate-to-marked insulin-induced hypoglycemia (IIH) is largely mediated by the autonomic nervous system. Because this glucagon response is impaired early in type 1 diabetes, we sought to determine if these patients, like animal models of autoimmune diabetes, have an early and severe loss of islet sympathetic nerves. We also tested whether this nerve loss is a permanent feature of type 1 diabetes, is islet-selective, and is not seen in type 2 diabetes. To do so, we quantified pancreatic islet and exocrine sympathetic nerve fiber area from autopsy samples of patients with type 1 or 2 diabetes and control subjects without diabetes. Our central finding is that patients with either very recent onset (<2 weeks) or long duration (>10 years) of type 1 diabetes have a severe loss of islet sympathetic nerves (Δ = −88% and Δ = −79%, respectively). In contrast, patients with type 2 diabetes lose no islet sympathetic nerves. There is no loss of exocrine sympathetic nerves in either type 1 or type 2 diabetes. We conclude that patients with type 1, but not type 2, diabetes have an early, marked, sustained, and islet-selective loss of sympathetic nerves, one that may impair their glucagon response to IIH. American Diabetes Association 2016-08 2016-05-13 /pmc/articles/PMC4955989/ /pubmed/27207540 http://dx.doi.org/10.2337/db16-0284 Text en © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
spellingShingle Islet Studies
Mundinger, Thomas O.
Mei, Qi
Foulis, Alan K.
Fligner, Corinne L.
Hull, Rebecca L.
Taborsky, Gerald J.
Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves
title Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves
title_full Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves
title_fullStr Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves
title_full_unstemmed Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves
title_short Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves
title_sort human type 1 diabetes is characterized by an early, marked, sustained, and islet-selective loss of sympathetic nerves
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955989/
https://www.ncbi.nlm.nih.gov/pubmed/27207540
http://dx.doi.org/10.2337/db16-0284
work_keys_str_mv AT mundingerthomaso humantype1diabetesischaracterizedbyanearlymarkedsustainedandisletselectivelossofsympatheticnerves
AT meiqi humantype1diabetesischaracterizedbyanearlymarkedsustainedandisletselectivelossofsympatheticnerves
AT foulisalank humantype1diabetesischaracterizedbyanearlymarkedsustainedandisletselectivelossofsympatheticnerves
AT flignercorinnel humantype1diabetesischaracterizedbyanearlymarkedsustainedandisletselectivelossofsympatheticnerves
AT hullrebeccal humantype1diabetesischaracterizedbyanearlymarkedsustainedandisletselectivelossofsympatheticnerves
AT taborskygeraldj humantype1diabetesischaracterizedbyanearlymarkedsustainedandisletselectivelossofsympatheticnerves