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AuthorBakkar, Nour-Mounira Z.
AuthorMougharbil, Nahed
AuthorMroueh, Ali
AuthorKaplan, Abdullah
AuthorEid, Ali H.
AuthorFares, Souha
AuthorZouein, Fouad A.
AuthorEl-Yazbi, Ahmed F.
Available date2023-09-06T05:27:57Z
Publication Date2020
Publication NameAmerican Journal of Physiology - Endocrinology and Metabolism
ResourceScopus
ISSN1931849
URIhttp://dx.doi.org/10.1152/ajpendo.00145.2020
URIhttp://hdl.handle.net/10576/47262
AbstractCardiac autonomic neuropathy (CAN) is an early cardiovascular manifestation of type 2 diabetes (T2D) that constitutes an independent risk factor for cardiovascular mortality and morbidity. Nevertheless, its underlying pathophysiology remains poorly understood. We recently showed that localized perivascular adipose tissue (PVAT) inflammation underlies the incidence of parasympathetic CAN in prediabetes. Here, we extend our investigation to provide a mechanistic framework for the evolution of autonomic impairment as the metabolic insult worsens. Early metabolic dysfunction was induced in rats fed a mild hypercaloric diet. Two low-dose streptozotocin injections were used to evoke a state of late decompensated T2D. Cardiac autonomic function was assessed by invasive measurement of baroreflex sensitivity using the vasoactive method. Progression into T2D was associated with aggravation of CAN to include both sympathetic and parasympathetic arms. Unlike prediabetic rats, T2D rats showed markers of brainstem neuronal injury and inflammation as well as increased serum levels of IL-1β. Experiments on PC12 cells differentiated into sympathetic-like neurons demonstrated that brainstem injury observed in T2D rats resulted from exposure to possible proinflammatory mediators in rat serum rather than a direct effect of the altered metabolic profile. CAN and the associated cardiovascular damage in T2D only responded to combined treatment with insulin to manage hyperglycemia in addition to a nonhypoglycemic dose of metformin or pioglitazone providing an anti-inflammatory effect, coincident with the effect of these combinations on serum IL-1β. Our present results indicate that CAN worsening upon progression to T2D involves brainstem inflammatory changes likely triggered by systemic inflammation.
SponsorThis work was supported by grant from the American University of Beirut, Faculty of Medicine, Medical Practice Plan (#320148) to A. F. El-Yazbi.
Languageen
PublisherAmerican Physiological Society
SubjectBrainstem inflammation
Cardiac autonomic neuropathy
Systemic inflammation
Type 2 diabetes
TitleWorsening baroreflex sensitivity on progression to type 2 diabetes: Localized vs. systemic inflammation and role of antidiabetic therapy
TypeArticle
PaginationE835-E851
Issue Number5
Volume Number319
dc.accessType Abstract Only


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