This presentation is showing the process of oxidative stress that occurs in patients having diabetes mellitus. A presentation for undergraduates.

1. Israa Kamel Mohamed Elaraby
Oxidative stress in diabetes Mellitus

2. Diabetes is usually accompanied by increased production of free
radicals or impaired antioxidant defenses

3. Mechanisms
of
hyperglycemia
induced
damage
Increased
polyol
pathway
flux
Advanced
glycation
end products
Activation
of protein
kinase c
Over
activity of
hexosamine
pathway

4. Increased polyol pathway flux
retina
glomerulus
Vascular cells
nerve
GSH , NO
cannot cross cell membrane
Osmotic stressOxidative stress

5. Advanced glycation end products (AGEs)
Proteins or lipids
Non-enzymatically
glycated after contact
with aldose sugars
Binding to RAGE
Upregulation of the transcription factor
nuclear factor-κB and its target genes.
Increases endothelial permeability to
macromolecules.
Block NO activity in the endothelium
-- oxidative stress

6. Activation of protein kinase C
ROS
Activity of GADPH
De-novo synthesis of DAG from
glucose via triose phosphate
Activation of PKC
Phosphorylation of
various proteins
Tissue injury
Ca++
phosphatidylserine

7. Overactivity of hexosamine pathway

8. A hypothesis in 2000 proved that all previous mechanisms are activated
by a single upstream event
Mitochondrial overproduction of the reactive oxygen species
(ROS)

9. Markers of oxidative stress
lipid Peroxidation
"highly reactive aldehydes, including MDA"
Protein Oxidation
"Advanced oxidation protein products (AOPPs),
protein carbonyls (PCO)"
Glutathione Level
Catalase
Superoxide Dismutase

10. Glycated hemoglobin (HbA1c)
Once a hemoglobin
molecule is glycated,
it remains that way
Measuring glycated hemoglobin
assesses the effectiveness of therapy by
monitoring long-term serum glucose
regulation
The HbA1c level is proportional to
average blood glucose concentration
over the previous four weeks to three
months.