Glucagon Pathway Offers New Treatments for Diabetes

by Mark Benson on April 18, 2012

New Pathway for Diabetes Management

The current way to maintain the right levels of sugar in the bloodstream is attributed to insulin. This hormone removes not only glucose but also the hormone glucagon. Glucagon helps in adding glucose.

This process has been done for many years in the treatment of Type II diabetes, focusing on insulin being present in the individual. A new study though has suggested that an even better approach would be to focus on the sweetening effect of glucagon.

These findings have been published in the online edition of the journal Cell Metabolism.

According to Dr. Ira Tabas, MD, PhD, the current Richard J. Stock Professor and Vice Chairman of Research for the Department of Medicine, “What we’ve found is a way to reduce glucagon’s influence on blood sugar without the side effects of global glucagon repression.” Dr. Tabas is also a professor of Anatomy and Cell Biology in Physiology and Cellular Biophysics and co-lead the research with Lale Ozcan, PhD, associate research scientist.

Glucagon was discovered at the same time as insulin but full research and investigation has been lukewarm and has remained behind the breakthroughs on insulin. The current treatments and medication have exclusively targeted the use of insulin.

The last decade though has seen that the success of incretins, which is a new class of drugs specifically for Type II diabetes has instigated renaissance into further research on the use and benefits of glucagon. At the outset, incretins were used to stimulate insulin secretion, although recent research has found that a significant aspect of the success is attributable to the previously unknown inhibiting effect of glucagon secretion on the body.

Now, with the new research on incretin, there is a new thrust for drugs that would work against glucagon, especially compounds that block glucagon in the liver. When in this organ, the glucagon then acts to become free glucose. Thus, drugs that block receptors in the liver have been tested but the versatility and multi-functionality of glucagon together with clinical trials to indicate if it can raise cholesterol and lead to fat deposits in the liver.

This new study has showcased how glucagon can affect glucose and disrupt its build up without remission of the other effects that glucagon provides the body. This phenomenon has shown promise in finding a safer and better anti-glucagon diabetes treatment.

The study authors further found that once glucagon binds to the receptor, glucose is released after an enzyme called CaMKII is activated. Once activated, CaMKII releases a protein named as Fox01 into the cell nucleus where it then turns on the genes that is much needed for glucose secretion. Another related pathway which works parallel to this, also sends a Fox01 helper protein into the cell nucleus. This was described in a paper where Dr. Tabas is a co-author, which was published online last April 8.

Dr. Tabas adds, “Even when their disease is well-controlled, most patients with Type II diabetes have excess glucagon action, so blocking CaMKII could potentially be a new way to lower blood sugar and better treat the disease.”

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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