TITLE:
Hyperglycemia Induced Changes in Vascular AKT3 May Inhibit Pressure-Induced Apoptosis in the Rat Inferior Venae Cavae
AUTHORS:
Kevin M. Rice, Ravi Kumar Arvapalli, Eric R. Blough
KEYWORDS:
Diabetes, Zucker Rat, Inferior Venae Cavae, AKT3
JOURNAL NAME:
Open Journal of Endocrine and Metabolic Diseases,
Vol.5 No.4,
April
23,
2015
ABSTRACT: Background: Vein graft failure after bypass surgery
is greatly increase in patients with diabetes mellitus. The cellular mechanisms
underlying the cause of this failure are largely unexplored. Protein kinase B/AKT
is a mechanically sensitive regulator of cellular growth and apoptosis. Herein
we examine whether diabetes affects the regulation of AKT in response to
increased venous loading. Methods: Inferior venae cavae (IVC) from the
non-diabetic lean (LNZ) and the diabetic obesesyndrome X Zucker(OSXZ) rats were isolated and incubated ex vivo under basal or pressurized conditions (120 mmHg). Protein
expression, basal activation and the ability of increased pressure to activate
AKT3 and apoptosis-related signaling were evaluated by immunoblot analysis.
Results: Compared to that seen in the non-diabetic lean animals, increased
venous pressure in the OSXZ rats was not characterized by increases in APAF-1
concentration, XIAP proteolysis, AIF cleavage, or Bad phosphorylation. This
evidence of decreased apoptotic signaling was associated with increased basal p-AKT3
levels (+136% ± 13% P