Na+/H+ exchanger 1 inhibition reverses manifestation of peripheral diabetic neuropathy in type 1 diabetic rats

Sergey Lupachyk; Pierre Watcho; Hanna Shevalye; Igor Vareniuk; Alexander Obrosov; Irina G Obrosova; Mark A Yorek

doi:10.1152/ajpendo.00186.2013

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Na+/H+ exchanger 1 inhibition reverses manifestation of peripheral diabetic neuropathy in type 1 diabetic rats

Journal article

Open access

Peer reviewed

Na+/H+ exchanger 1 inhibition reverses manifestation of peripheral diabetic neuropathy in type 1 diabetic rats

Sergey Lupachyk, Pierre Watcho, Hanna Shevalye, Igor Vareniuk, Alexander Obrosov, Irina G Obrosova and Mark A Yorek

American journal of physiology: endocrinology and metabolism, Vol.305(3), pp.E396-404

08/01/2013

DOI: 10.1152/ajpendo.00186.2013

PMCID: PMC3742852

PMID: 23736542

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Abstract

Evidence for an important role for Na(+)/H(+) exchangers in diabetic complications is emerging. The aim of this study was to evaluate whether Na(+)/H(+) exchanger 1 inhibition reverses experimental peripheral diabetic neuropathy. Control and streptozotocin-diabetic rats were treated with the specific Na(+)/H(+) exchanger 1 inhibitor cariporide for 4 wk after 12 wk without treatment. Neuropathy end points included sciatic motor and sensory nerve conduction velocities, endoneurial nutritive blood flow, vascular reactivity of epineurial arterioles, thermal nociception, tactile allodynia, and intraepidermal nerve fiber density. Advanced glycation end product and markers of oxidative stress, including nitrated protein levels in sciatic nerve, were evaluated by Western blot. Rats with 12-wk duration of diabetes developed motor and sensory nerve conduction deficits, thermal hypoalgesia, tactile allodynia, and intraepidermal nerve fiber loss. All these changes, including impairment of nerve blood flow and vascular reactivity of epineurial arterioles, were partially reversed by 4 wk of cariporide treatment. Na(+)/H(+) exchanger 1 inhibition was also associated with reduction of diabetes-induced accumulation of advanced glycation endproduct, oxidative stress, and nitrated proteins in sciatic nerve. In conclusion, these findings support an important role for Na(+)/H(+) exchanger 1 in functional, structural, and biochemical manifestations of peripheral diabetic neuropathy and provide the rationale for development of Na(+)/H(+) exchanger 1 inhibitors for treatment of diabetic vascular and neural complications.

Aldehydes - metabolism

Animals

Arterioles - physiopathology

Behavior, Animal - drug effects

Blood Glucose - metabolism

Blotting, Western

Body Weight - drug effects

Diabetes Mellitus, Experimental - physiopathology

Diabetes Mellitus, Type 1 - complications

Diabetic Neuropathies - drug therapy

Diabetic Neuropathies - psychology

Glycation End Products, Advanced - metabolism

Guanidines - pharmacology

Guanidines - therapeutic use

Male

Nerve Fibers - physiology

Nitrates - metabolism

Pain Measurement - drug effects

Pyruvaldehyde - metabolism

Rats

Rats, Wistar

Reduced Folate Carrier Protein - antagonists & inhibitors

Sciatic Nerve - drug effects

Sciatic Nerve - metabolism

Skin - innervation

Sulfones - pharmacology

Sulfones - therapeutic use

Superoxides - metabolism

Tyrosine - analogs & derivatives

Tyrosine - metabolism

Details

Title: Subtitle: Na+/H+ exchanger 1 inhibition reverses manifestation of peripheral diabetic neuropathy in type 1 diabetic rats
Creators: Sergey Lupachyk - Louisiana State University System
Pierre Watcho - Louisiana State University System
Hanna Shevalye - Louisiana State University System
Igor Vareniuk - Louisiana State University System
Alexander Obrosov - Louisiana State University System
Irina G Obrosova - Louisiana State University System
Mark A Yorek - United States Department of Veterans Affairs
Resource Type: Journal article
Publication Details: American journal of physiology: endocrinology and metabolism, Vol.305(3), pp.E396-404
DOI: 10.1152/ajpendo.00186.2013
PMID: 23736542
PMCID: PMC3742852
ISSN: 0193-1849
eISSN: 1522-1555
Grant note: DK-077141 / NIDDK NIH HHS DK-073990 / NIDDK NIH HHS
Language: English
Date published: 08/01/2013
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9984359853402771

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