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Dietary Blueberries Attenuate Vascular Inflammation and Dysfunction in Diabetic db/db Mice
Author(s) -
Bharat Divya,
Petersen Chrissa,
Gholami Samira,
Denetso Christopher,
Cutler Brett,
Kim JiSeok,
Symons J David,
Velayutham Anandh Babu Pon
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.166.2
Subject(s) - medicine , endocrinology , diabetes mellitus , blood pressure , insulin , ex vivo , mesenteric arteries , inflammation , endothelial dysfunction , in vivo , artery , biology , microbiology and biotechnology
Background Patients with diabetes are 2–4 fold more susceptible to cardiovascular complications. High glucose‐induced vascular inflammation and the subsequent vascular dysfunction play a major role in the development of atherosclerosis in the context of diabetes. In preliminary studies we showed that relative to vehicle (BSA) treated arteries, dysfunction was less severe in segments that incubated 18–24 h with palmitate + blueberry metabolites vs. palmitate alone. Based on these data from arterial segments treated ex vivo with blueberry metabolites, we tested the hypothesis that blueberry supplementation attenuates vascular complications in diabetic db/db mice. Methods Seven week old male diabetic db/db mice that consumed standard chow ( db/db ) or chow supplemented with 3.8% freeze‐dried blueberries ( db/db +BB) for 10 weeks were compared to non‐diabetic control mice ( db/+ ). Based on normalization to body surface area, this dose in mice is equivalent to ~1.5 servings of BB (~240 g) in humans. At ~17 weeks the following in vivo analyses were completed: (i) body weight and food intake; (ii) glucose (GTT) and insulin (ITT) tolerance; and (iii) systemic arterial blood pressure (tail cuff). Ex vivo analyses included the assessment of vascular inflammation (fluorescent labeled monocyte binding to aortic endothelium), and determination of mesenteric arterial reactivity (isometric tension procedures). Results Compared to db/+ animals, both diabetic groups displayed similar increases (p<0.05) in weight gain and impairments (p<0.05) in glucose and insulin tolerance. Arterial pressure (systolic, diastolic, and mean) was higher (p<0.05) in db/db vs. db/+ mice, but the severity of hypertension was attenuated (p<0.05) in db/db +BB mice. After precontraction with ~ 10 −6 M phenylephrine, acetylcholine (ACh; 10 −8 –10 −6 M) evoked vasorelaxation was impaired (p<0.05) in db/db vs. db/+ animals, but no differences existed between db/db +BB vs. db/+ mice. Vasorelaxation to sodium nitroprusside (10 −9 –10 −4 M) was complete and similar among groups. Fluorescent‐labeled mouse monocyte WEHI 78/24 cells exhibited higher (p<0.05) binding to aortic endothelium from db/db vs. db/+ mice, but this response was reduced (p<0.05) in aortic endothelium from db/db +BB mice. Ongoing studies are focused on identifying the effect of blueberries on inflammatory molecules in the vasculature, and exploring the molecular signaling mechanisms responsible for the protective effects of blueberries. Conclusion Blueberry consumption may be a potential adjunct therapy to prevent, delay, and/or limit the severity of vascular complications in diabetes. Support or Funding Information Supported by University of Utah Seed Grant and College of Health Research Pilot Grant.