Diabetes: A Precursor to Cardiovascular

Complications
Increased NADPH oxidase activity Impaired mitochondrial ETC system

Diabetes is acknowledged as a precursor for cardiovascular complications. Endothelial cardiovascular tissue taken from non-obese diabetic rats were studied. The mechanism by which diabetes prompts cardiovascular complications , however, is yet to be revealed. The current study proposes a part of the answer, summarized in the figure to the right.

Heightened Oxidative Stress

An increase in phosphorylation in cardiovascular endothelial cytosol

Ratio of phospohorylation in comparison to the control
180% 160% 140% 120% 100% 80% 60% 40% 20% 0% Control Diabetes Diabetes Diabetic + treated with ALA + WM ALA

NF-B and mitochondrial activation of DNA transcription

IkB IKK ( and ) NiK

Tumor necrosis factor-, ICAM, fractalkine, CF68, myeloperoxidase

Low grade inflammation

Type II diabetic non-obese rat groups CVS endothelial dysfunction

In cardiovascular endothelial tissues of diabetic rats, a marked cytosolic phospohorylation hype is found.

The proposed roleplayers in turning diabetes into a cardiovascular problem are: NADPH oxidase TNF-alpha
Endothelial aortic tissue relaxation response to in vitro acetylcholine in different environments Degree of endothelial vasodilatation
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% -8 -7 -6 -5 -4

Inflammation indicators in endothelial aortic tissues mRNA-based indicator-measure as a ratio to the control group
250% 200% 150% 100% 50% 0% Diabetics Diabetics + ALA Control Diabetics + ALA & WM

Non-diabetic controls Diabetics

Treated diabetics

Type II diabetic non-obese rat groups

Treated diabetics and wortmannininhibited Increasing amount of Ach induction (log mol/L)

Inflammation indicators in cytosolic endothelial tissues are significantly depleted when Lipoic acid was present.

Relaxation of endothelial cells as a response to acetylcholine is compromised in the diabetics. It is restored by the injection of Lipoic acid.
References
1.Bitar, MS et al. (2010) Inflammation and apoptosis in aortic tissues of aged type II diabetes: amelioration with -lipoid acid through phosphatidulinositol 3-kinase/Akt-dependent mechanism.