Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes

Abstract Dysregulation of glucagon secretion in type 1 diabetes (T1D) involves hypersecretion during postprandial states, but insufficient secretion during hypoglycemia. The sympathetic nervous system regulates glucagon secretion. To investigate islet sympathetic innervation in T1D, sympathetic tyro...

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Autores principales:	Martha Campbell-Thompson, Elizabeth A. Butterworth, J. Lucas Boatwright, Malavika A. Nair, Lith H. Nasif, Kamal Nasif, Andy Y. Revell, Alberto Riva, Clayton E. Mathews, Ivan C. Gerling, Desmond A. Schatz, Mark A. Atkinson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/06c0546e7343448f81538ebc42c845a0
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spelling	oai:doaj.org-article:06c0546e7343448f81538ebc42c845a02021-12-02T16:35:56ZIslet sympathetic innervation and islet neuropathology in patients with type 1 diabetes10.1038/s41598-021-85659-82045-2322https://doaj.org/article/06c0546e7343448f81538ebc42c845a02021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85659-8https://doaj.org/toc/2045-2322Abstract Dysregulation of glucagon secretion in type 1 diabetes (T1D) involves hypersecretion during postprandial states, but insufficient secretion during hypoglycemia. The sympathetic nervous system regulates glucagon secretion. To investigate islet sympathetic innervation in T1D, sympathetic tyrosine hydroxylase (TH) axons were analyzed in control non-diabetic organ donors, non-diabetic islet autoantibody-positive individuals (AAb), and age-matched persons with T1D. Islet TH axon numbers and density were significantly decreased in AAb compared to T1D with no significant differences observed in exocrine TH axon volume or lengths between groups. TH axons were in close approximation to islet α-cells in T1D individuals with long-standing diabetes. Islet RNA-sequencing and qRT-PCR analyses identified significant alterations in noradrenalin degradation, α-adrenergic signaling, cardiac β-adrenergic signaling, catecholamine biosynthesis, and additional neuropathology pathways. The close approximation of TH axons at islet α-cells supports a model for sympathetic efferent neurons directly regulating glucagon secretion. Sympathetic islet innervation and intrinsic adrenergic signaling pathways could be novel targets for improving glucagon secretion in T1D.Martha Campbell-ThompsonElizabeth A. ButterworthJ. Lucas BoatwrightMalavika A. NairLith H. NasifKamal NasifAndy Y. RevellAlberto RivaClayton E. MathewsIvan C. GerlingDesmond A. SchatzMark A. AtkinsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martha Campbell-Thompson Elizabeth A. Butterworth J. Lucas Boatwright Malavika A. Nair Lith H. Nasif Kamal Nasif Andy Y. Revell Alberto Riva Clayton E. Mathews Ivan C. Gerling Desmond A. Schatz Mark A. Atkinson Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes
description	Abstract Dysregulation of glucagon secretion in type 1 diabetes (T1D) involves hypersecretion during postprandial states, but insufficient secretion during hypoglycemia. The sympathetic nervous system regulates glucagon secretion. To investigate islet sympathetic innervation in T1D, sympathetic tyrosine hydroxylase (TH) axons were analyzed in control non-diabetic organ donors, non-diabetic islet autoantibody-positive individuals (AAb), and age-matched persons with T1D. Islet TH axon numbers and density were significantly decreased in AAb compared to T1D with no significant differences observed in exocrine TH axon volume or lengths between groups. TH axons were in close approximation to islet α-cells in T1D individuals with long-standing diabetes. Islet RNA-sequencing and qRT-PCR analyses identified significant alterations in noradrenalin degradation, α-adrenergic signaling, cardiac β-adrenergic signaling, catecholamine biosynthesis, and additional neuropathology pathways. The close approximation of TH axons at islet α-cells supports a model for sympathetic efferent neurons directly regulating glucagon secretion. Sympathetic islet innervation and intrinsic adrenergic signaling pathways could be novel targets for improving glucagon secretion in T1D.
format	article
author	Martha Campbell-Thompson Elizabeth A. Butterworth J. Lucas Boatwright Malavika A. Nair Lith H. Nasif Kamal Nasif Andy Y. Revell Alberto Riva Clayton E. Mathews Ivan C. Gerling Desmond A. Schatz Mark A. Atkinson
author_facet	Martha Campbell-Thompson Elizabeth A. Butterworth J. Lucas Boatwright Malavika A. Nair Lith H. Nasif Kamal Nasif Andy Y. Revell Alberto Riva Clayton E. Mathews Ivan C. Gerling Desmond A. Schatz Mark A. Atkinson
author_sort	Martha Campbell-Thompson
title	Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes
title_short	Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes
title_full	Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes
title_fullStr	Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes
title_full_unstemmed	Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes
title_sort	islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/06c0546e7343448f81538ebc42c845a0
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Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes

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