Journal article
Combination therapies prevent the neuropathic, proinflammatory characteristics of bone marrow in streptozotocin-induced diabetic rats
Diabetes (New York, N.Y.), Vol.64(2), pp.643-653
02/2015
DOI: 10.2337/db14-0433
PMCID: PMC4876792
PMID: 25204979
Abstract
We previously showed that peripheral neuropathy of the bone marrow was associated with loss of circadian rhythmicity of stem/progenitor cell release into the circulation. Bone marrow neuropathy results in dramatic changes in hematopoiesis that lead to microvascular complications, inflammation, and reduced endothelial repair. This series of events represents early pathogenesis before development of diabetic retinopathy. In this study we characterized early alterations within the bone marrow of streptozotocin (STZ)-induced diabetic rats following treatments that prevent experimental peripheral neuropathy. We asked whether bone marrow neuropathy and the associated bone marrow pathology were reversed with treatments that prevent peripheral neuropathy. Three strategies were tested: inhibition of neutral endopeptidase, inhibition of aldose reductase plus lipoic acid supplementation, and insulin therapy with antioxidants. All strategies prevented loss of nerve conduction velocity resulting from STZ-induced diabetes and corrected the STZ-induced diabetes-associated increase of immunoreactivity of neuropeptide Y, tyrosine hydroxylase, and somatostatin. The treatments also reduced concentrations of interleukin-1β, granulocyte colony-stimulating factor, and matrix metalloproteinase 2 in STZ-induced diabetic bone marrow supernatant and decreased the expression of NADPH oxidase 2, nitric oxide synthase 2, and nuclear factor-κB1 mRNA in bone marrow progenitor cells. These therapies represent novel approaches to attenuate the diabetic phenotype within the bone marrow and may constitute an important therapeutic strategy for diabetic microvascular complications.
Details
- Title: Subtitle
- Combination therapies prevent the neuropathic, proinflammatory characteristics of bone marrow in streptozotocin-induced diabetic rats
- Creators
- James M Dominguez II - Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FLMark A Yorek - Iowa City VA Health Care SystemMaria B Grant - Indiana University
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.64(2), pp.643-653
- DOI
- 10.2337/db14-0433
- PMID
- 25204979
- PMCID
- PMC4876792
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Grant note
- I01 BX001680 / BLRD VA R01 HL110170 / NHLBI NIH HHS R01 DK090730 / NIDDK NIH HHS R01 EY012601 / NEI NIH HHS R01 EY007739 / NEI NIH HHS
- Language
- English
- Date published
- 02/2015
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359764502771
Metrics
8 Record Views