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Na+/H+ exchanger 1 inhibition reverses manifestation of peripheral diabetic neuropathy in type 1 diabetic rats.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2013 Aug 01; Vol. 305 (3), pp. E396-404. Date of Electronic Publication: 2013 Jun 04. - Publication Year :
- 2013
-
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.
- Subjects :
- Aldehydes metabolism
Animals
Arterioles physiopathology
Behavior, Animal drug effects
Blood Glucose metabolism
Blotting, Western
Body Weight drug effects
Diabetes Mellitus, Experimental physiopathology
Diabetic Neuropathies psychology
Glycation End Products, Advanced metabolism
Guanidines pharmacology
Male
Nerve Fibers physiology
Nitrates metabolism
Pain Measurement drug effects
Pyruvaldehyde metabolism
Rats
Rats, Wistar
Sciatic Nerve drug effects
Sciatic Nerve metabolism
Skin innervation
Sulfones pharmacology
Superoxides metabolism
Tyrosine analogs & derivatives
Tyrosine metabolism
Diabetes Mellitus, Type 1 complications
Diabetic Neuropathies drug therapy
Guanidines therapeutic use
Reduced Folate Carrier Protein antagonists & inhibitors
Sulfones therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 305
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 23736542
- Full Text :
- https://doi.org/10.1152/ajpendo.00186.2013