Autonomic neuropathy in experimental models of diabetes mellitus

Schmidt, Robert E.

doi:10.1016/b978-0-444-53480-4.00038-2

Cited by 17 publications

(11 citation statements)

References 264 publications

(198 reference statements)

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“…M 1 antagonism also removes a constraint on microtubule polymerization and mitochondrial trafficking and promotes a biased β-arrestin dependent ERK-CREB signal so that both blocking growth-impeding signals and initiating other signaling cascades may contribute to neuroprotection. Whether autonomic neuropathy (Schmidt, 2014) is afforded similar protection remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Topical Delivery of Muscarinic Receptor Antagonists Prevents and Reverses Peripheral Neuropathy in Female Diabetic Mice

Jolivalt¹,

Frizzi²,

Han³

et al. 2020

J Pharmacol Exp Ther

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Muscarinic antagonists promote sensory neurite outgrowth in vitro and prevent and/or reverse multiple indices of peripheral neuropathy in rodent models of diabetes, chemotherapy-induced peripheral neuropathy and HIV protein-induced neuropathy when delivered systemically. We measured plasma concentrations of the M 1 receptor selective muscarinic antagonist pirenzepine when delivered by sub-cutaneous injection, oral gavage or topical application to the skin and investigated efficacy of topically delivered pirenzepine against indices of peripheral neuropathy in diabetic mice. Topical application of 2% pirenzepine to the paw resulted in plasma concentrations 6hr postdelivery that approximated those previously shown to promote neurite outgrowth in vitro. Topical delivery of pirenzepine to the paw of streptozotocin-diabetic mice dosedependently (0.1-10.0%) prevented tactile allodynia, thermal hypoalgesia and loss of epidermal nerve fibers in the treated paw and attenuated large fiber motor nerve conduction slowing in the ipsilateral limb. Efficacy against some indices of neuropathy was also noted in the contralateral limb, indicating systemic effects following local treatment. Topical pirenzepine also reversed established paw heat hypoalgesia while withdrawal of treatment resulted in a gradual decline in efficacy over 2-4 weeks. Efficacy of topical pirenzepine was muted when treatment was reduced from 5 to 3 or 1 days per week. Similar local effects were noted with the non-selective muscarinic receptor antagonist atropine when applied either to the paw or to the eye. Topical delivery of muscarinic antagonists may serve as a practical therapeutic approach to treating diabetic and other peripheral neuropathies.

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Section: Discussionmentioning

confidence: 99%

Topical Delivery of Muscarinic Receptor Antagonists Prevents and Reverses Peripheral Neuropathy in Female Diabetic Mice

Jolivalt¹,

Frizzi²,

Han³

et al. 2020

J Pharmacol Exp Ther

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“…The expression of advanced glycation end products (AGEs) and their receptor (RAGE) was upregulated in the esophageal mucosa and muscle layers in diabetic rats . DM‐induced histological changes of autonomic nerves, including the vagus nerve, have been demonstrated in other parts of the GI tract . However, such data are limited in relation to the esophagus in DM animal models.…”

Section: Diabetes‐induced Remodeling In the Esophagusmentioning

confidence: 99%

“…63 DM-induced histological changes of autonomic nerves, including the vagus nerve, have been demonstrated in other parts of the GI tract. 15,[64][65][66] However, such data are limited in relation to the esophagus in DM animal models. esophageal wall stiffness.…”

Section: Parametersmentioning

confidence: 99%

Diabetes‐induced mechanophysiological changes in the esophagus

Zhao

Gregersen

2016

Annals of the New York Academy of Sciences

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Esophageal disorders are common in diabetes mellitus (DM) patients. DM induces mechanostructural remodeling in the esophagus of humans and animal models. The remodeling is related to esophageal sensorimotor abnormalities and to symptoms frequently encountered by DM patients. For example, gastroesophageal reflux disease (GERD) is a common disorder associated with DM. This review addresses diabetic remodeling of esophageal properties and function in light of the Esophagiome, a scientifically based modeling effort to describe the physiological dynamics of the normal, intact esophagus built upon interdisciplinary approaches with applications for esophageal disease. Unraveling the structural, biomechanical, and sensory remodeling of the esophagus in DM must be based on a multidisciplinary approach that can bridge the knowledge from a variety of scientific disciplines. The first focus of this review is DM-induced morphodynamic and biomechanical remodeling in the esophagus. Second, we review the sensorimotor dysfunction in DM and how it relates to esophageal remodeling. Finally, we discuss the clinical consequences of DM-induced esophageal remodeling, especially in relation to GERD. The ultimate aim is to increase the understanding of DM-induced remodeling of esophageal structure and sensorimotor function in order to assist clinicians to better understand the esophageal disorders induced by DM and to develop better treatments for those patients.

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“…Studies of parasympathetic ganglia and projections suggest the selective loss of nitrergic innervation of the stomach and penis of diabetic rodents, which shows a biphasic degenerative response: initially insulin-reversible loss of axonal nitric oxide synthase (NOS) and later irreversible neuron loss [28]. In other diabetic animal models, subpopulations of autonomic fibers within the gut, bladder, penis, and other end organs may show preferential damage [29].…”

Section: Pathologymentioning

confidence: 99%