Journal article
Interleukin-10 protects nitric oxide-dependent relaxation during diabetes: role of superoxide
Diabetes (New York, N.Y.), Vol.51(6), pp.1931-1937
06/2002
DOI: 10.2337/diabetes.51.6.1931
PMID: 12031983
Abstract
Interleukin (IL)-10, an anti-inflammatory cytokine, preserves endothelial function during acute inflammation. We tested the hypotheses that IL-10 plays a protective role in blood vessels during diabetes by suppressing impairment of endothelium-dependent relaxation and that protection by IL-10 is mediated by effects on superoxide (O(2-)). Streptozotocin (150 mg/kg i.p.) or citrate buffer was injected into IL-10-deficient (IL-10(-/-)) mice and wild-type controls (IL-10(+/+)). In IL-10(+/+) and IL-10(-/-) mice, blood glucose levels were approximately 120 mg/dl after citrate administration and approximately 400 mg/dl after streptozotocin administration. Vasorelaxation was examined in arteries in vitro 12-16 weeks later. Maximum relaxation to acetylcholine (30 micromol/l) was 88 +/- 3% (means +/- SE) in nondiabetic mice and 84 +/- 3% in diabetic IL-10(+ /+) mice (P > 0.05). Thus, at this time point, diabetes did not impair endothelium-dependent relaxation in vessels in wild-type mice. In contrast, maximum relaxation in vessels from diabetic IL-10(-/-) mice was significantly decreased (74 +/- 5%) compared with nondiabetic IL-10(-/-) mice (93 +/- 2%, P < 0.05). Superoxide dismutase with polyethylene glycol (PEG-SOD) restored impaired responses to acetylcholine to levels seen in controls. Responses to acetylcholine also were improved by allopurinol (an inhibitor of xanthine oxidase) in vessels from diabetic IL-10(- /-) mice. Thus, diabetes produces greater impairment of relaxation to acetylcholine in IL-10(-/-) mice than in IL-10(+/ +) mice. These findings provide direct evidence that IL-10 impedes mechanisms of endothelial dysfunction during diabetes. Restoration of vasorelaxation with PEG-SOD or allopurinol suggests that the mechanism(s) by which IL-10 preserves endothelium-dependent vasorelaxation involves O(2-), perhaps by reducing production of O(2-) by xanthine oxidase.
Details
- Title: Subtitle
- Interleukin-10 protects nitric oxide-dependent relaxation during diabetes: role of superoxide
- Creators
- Carol A Gunnett - Department of Internal Medicine, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa 52242-1081, USA. carol-gunnett@uiowa.eduDonald D HeistadFrank M Faraci
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.51(6), pp.1931-1937
- Publisher
- United States
- DOI
- 10.2337/diabetes.51.6.1931
- PMID
- 12031983
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Grant note
- HL-16066 / NHLBI NIH HHS HL-38901 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS HL14388 / NHLBI NIH HHS HL-62984 / NHLBI NIH HHS
- Language
- English
- Date published
- 06/2002
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040561902771
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