GPX1, SOD1 and Type II DiabetesA brief introduction and survey of current research

Why is our research important?

Diabetes is:A major cause of heart disease and strokeThe seventh leading cause of death in the United StatesResponsible for $116 billion in direct medical costsIncurable at present, but treatable

Understanding the complex mechanisms and processes that cause, mitigate or could prevent the onset of type II diabetes will help us better treat and possibly cure the disease.

The more we know, the more we can do.

What is type II diabetes?~90% of all cases of diabetes are type II

Insulin resistance within muscles + fat tissue and inadequate insulin production to compensate high blood glucose = complications!

Key hormone: INSULIN

Not for a type

II diabet

es suffere

r

Molecular mechanism of insulin

What is important to us about insulin?

An insulin hexamer.

Produced in pancreas in islets of Langerhans

Amino acid-sequence of insulin extremely well preserved within vertebrates

Complex regulatory system, metabolic pathway and release regime (ideas!)

Cause and molecular mechanisms of insulin resistance a subject of intense research!

What is glutathione peroxidase 1 (GPX1)?

“gloot-a-thigh-own”

One of the most important antioxidant enzymes in humans, detoxifies hydrogen peroxide (H2O2), which is an oxidative species

An intracellular selenoproteinOxidative stress associated with insulin resistance (IDEA!) GPX1 linked to development of insulin resistance and obesity in mice that overexpress it!

What is superoxide dismutase 1 (SOD1)?

Another important antioxidant enzyme responsible for destroying free superoxide radicals in the body

Knockout of SOD1 in mice reduces insulin function and also bone strength! how could this be exploited to help treat diabetes?

A very simplified molecular pathway

Superoxide anion

via SOD1 enzyme

via GPX1 enzyme

Hydrogen peroxide

(H2O2)

Water (H2O)

Bad news! Good news!Still bad news!

More antioxidant enzyme studies

What are we doing now?Dr. Jun Won Yun, Postdoctoral associate at Cornell Department of Animal Science, Lei Lab

What role does selenium have on GPX1 enzyme activity and also insulin secretion/insulin resistance?

Recall GPX1 is a selenoprotein and is dependent on selenium

Thank you for listening!