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Publication
Mesenteric arterial dysfunction in the UC Davis Type 2 Diabetes Mellitus rat
model is dependent on pre-diabetic versus diabetic status and is sexually
dimorphic.
Authors Shaligram S, Akther F, Razan MR, Graham JL, Roglans N, Alegret M, Parsa AG,
Stanhope KL, Havel PJ, Rahimian R
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal European journal of pharmacology
Year 2020
Date Published 7/1/2020
Volume : Pages 879 : 173089
PubMed Reference 32320701
Abstract Previous reports suggest that diabetes may differentially affect the vascular
beds of females and males. However, there is insufficient evidence to establish
the timeline of the vascular dysfunction in diabetes, specifically in relation
to sex. Here, we determined whether mesenteric arterial function is altered in
UC Davis Type-2 Diabetes Mellitus (UCD-T2DM) rats and if this occurs as early as
the pre-diabetic stage of the disease. Specifically, we investigated whether
vascular dysfunction differs between pre-diabetic or diabetic status and if this
varies by sex. We measured the responses to endothelium-dependent and
-independent vasorelaxant as well as vasoconstrictor agents and explored the
potential mechanisms involved in sex-specific development of arterial
dysfunction in UCD-T2DM rats. In addition, indices of insulin sensitivity were
assessed. We report the reduced insulin sensitivity in pre-diabetic males and
diabetic females. Vascular relaxation to acetylcholine was impaired to a greater
extent in mesenteric artery from males in the pre-diabetic stage than in their
female counterparts. In contrast, the arteries from females with diabetes
exhibited a greater impairment to acetylcholine compared with diabetic males.
Additionally, the sensitivity of mesenteric artery to contractile agents in
females, but not in males, after the onset of diabetes was increased. Our data
suggest that the reduced insulin sensitivity through AKT may predispose vessels
to injury in the pre-diabetic stage in males. On the other hand, reduced insulin
sensitivity as well as enhanced responsiveness to contractile agents may
predispose arteries to injury in the diabetic stage in females.




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