Pancreatic nerve electrostimulation inhibits recent-onset autoimmune diabetes

Guyot, Mélanie; Thézenas, Simon; Ceppo, Franck; Panzolini, Clara; Guyon, Alice; Lavergne, Julien; Murris, Emilie; Daoudlarian, Douglas; Brusini, Romain; Zarif, Hadi; Abélanet, Sophie; Hugues-Ascery, Sandrine; Divoux, Jean-Louis; Lewis, Stephen J.; Sridhar, Arun; Glaichenhaus, Nicolas

doi:10.1038/s41587-019-0295-8

Cited by 38 publications

(34 citation statements)

References 22 publications

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“…http://advances.sciencemag.org/ Downloaded from pancreas were targeted with electrostimulation and were able to show decreased incidence of T1D in the NOD mouse (31). Targeting local organ innervation may be a way to take the field further, especially because recent advances in materials technology could potentially allow for the development of miniaturized implantable electrostimulators (31). The influence of pancreatic innervation on T1D pathogenesis has not yet been evaluated to any great extent.…”

Section: Discussionmentioning

confidence: 99%

“…Vagal stimulation may have off-target effects due to the vast afferent and efferent reach of this nerve and might therefore not be suitable for T1D treatment. A recent study in mice took a different approach where sympathetic nerves projecting into lymph nodes draining the pancreas were targeted with electrostimulation and were able to show decreased incidence of T1D in the NOD mouse ( 31 ). Targeting local organ innervation may be a way to take the field further, especially because recent advances in materials technology could potentially allow for the development of miniaturized implantable electrostimulators ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

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Interference with pancreatic sympathetic signaling halts the onset of diabetes in mice

2020

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The notably lobular distribution of immune lesions in type 1 diabetes (T1D) has been hypothesized to be the result of innervation within the pancreas. To investigate whether neuroimmune interactions could explain this phenomenon, we explored the impact of sympathetic signaling in the RIP-LCMV-GP mouse model of autoimmune diabetes. In this model, the CD8+ T cell attack on β cells replicates a key pathogenic feature of human T1D. We found that inhibition of α1 adrenoceptors, ablation of sympathetic nerves, and surgical denervation all had a protective effect in this model, without affecting the systemic presence of β cell–reactive CD8+ T cells. In vivo multiphoton imaging revealed a local effect within pancreatic islets including limited infiltration of both macrophages and β cell–specific CD8+ T cells. Islet-resident macrophages expressed adrenoceptors and were responsive to catecholamines. Islet macrophages may therefore constitute a pivotal neuroimmune signaling relay and could be a target for future interventions in T1D.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Interference with pancreatic sympathetic signaling halts the onset of diabetes in mice

2020

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“…Sympathetic activation leads to vasoconstriction, reduces exocrine secretion, and shifts endocrine secretion to the hyperglycemic state by lowering insulin and increasing glucagon levels ( 44 , 45 ). In addition to this canonical sympathetic effect on pancreatic secretory function, several recent studies report an important interaction of sympathetic innervation with the pancreatic immune system ( 14 , 46 , 47 ), which could be involved in the development of autoimmune diabetes ( 48 ).…”

Section: Structural and Functional Features Of Pancreatic Innervationmentioning

confidence: 99%

“…Perhaps investigators were not motivated to do so because of the common notion that sympathetic stimulation induces a uniform inhibitory effect on digestion. Recent studies, however, are revealing an important interaction of sympathetic nerves with the immune system, particularly with immune cells of lymph nodes associated with the pancreas ( 14 , 46 , 47 ). A characterization of postganglionic sympathetic neurons therefore becomes physiologically and even clinically relevant.…”

Section: Live Imaging Of Pancreatic Innervationmentioning

confidence: 99%

Optical Imaging of Pancreatic Innervation

Makhmutova

Caicedo

2021

Front. Endocrinol.

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At the time of Ivan Pavlov, pancreatic innervation was studied by looking at pancreas secretions in response to electrical stimulation of nerves. Nowadays we have ways to visualize neuronal activity in real time thanks to advances in fluorescent reporters and imaging techniques. We also have very precise optogenetic and pharmacogenetic approaches that allow neuronal manipulations in a very specific manner. These technological advances have been extensively employed for studying the central nervous system and are just beginning to be incorporated for studying visceral innervation. Pancreatic innervation is complex, and the role it plays in physiology and pathophysiology of the organ is still not fully understood. In this review we highlight anatomical aspects of pancreatic innervation, techniques for pancreatic neuronal labeling, and approaches for imaging pancreatic innervation in vitro and in vivo.

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“…The impact of neurostimulation on type 1 diabetes has been less explored, but recent research from Guyot et al (2019) suggests that stimulation of the pancreatic sympathetic nerves projecting to the pancreatic lymph nodes inhibits the progression of the disease, at least in mice (Guyot et al 2019). Activation of these nerves with a stimulation frequency of 10 Hz and 450 μA amplitude resulted in a reduction of pro-inflammatory cytokines and of the proliferation of autoreactive T cells, therefore limiting the progression of the disease.…”

Section: State Of the Artmentioning

confidence: 99%

Closed-loop bioelectronic medicine for diabetes management

2020

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Modulation of the nervous system by delivering electrical or pharmaceutical agents has contributed to the development of novel treatments to serious health disorders. Recent advances in multidisciplinary research has enabled the emergence of a new powerful therapeutic approach called bioelectronic medicine. Bioelectronic medicine exploits the fact that every organ in our bodies is neurally innervated and thus electrical interfacing with peripheral nerves can be a potential pathway for diagnosing or treating diseases such as diabetes. In this context, a plethora of studies have confirmed the important role of the nervous system in maintaining a tight regulation of glucose homeostasis. This has initiated new research exploring the opportunities of bioelectronic medicine for improving glucose control in people with diabetes, including regulation of gastric emptying, insulin sensitivity, and secretion of pancreatic hormones. Moreover, the development of novel closed-loop strategies aims to provide effective, specific and safe interfacing with the nervous system, and thereby targeting the organ of interest. This is especially valuable in the context of chronic diseases such as diabetes, where closed-loop bioelectronic medicine promises to provide real-time, autonomous and patient-specific therapies. In this article, we present an overview of the state-of-the-art for closed-loop neuromodulation systems in relation to diabetes and discuss future related opportunities for management of this chronic disease.

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Pancreatic nerve electrostimulation inhibits recent-onset autoimmune diabetes

Cited by 38 publications

References 22 publications

Interference with pancreatic sympathetic signaling halts the onset of diabetes in mice

Interference with pancreatic sympathetic signaling halts the onset of diabetes in mice

Optical Imaging of Pancreatic Innervation

Closed-loop bioelectronic medicine for diabetes management

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