Stress and Diabetes, A Cellular Connection

Stress and diabetes
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Stress is often blamed or associated with a number of health issues ranging from gastrointestinal problems to depression and migraines. Now researchers at the University of California, San Francisco (UCSF) say they have found how a protein plays a significant role in the relationship between stress and diabetes at a cellular level.

How important is stress in diabetes?

When you hear the word "stress," what do you think of? Working late at the office? Trying to meet a deadline? Getting caught in hours of traffic? Dealing with a screaming baby all night? Although these are all examples of stressful situations, the type of stress associated with diabetes is at a cellular level and is critical because it can result in a failure to produce insulin, and thus lead to the development of diabetes.

At UCSF, scientists found that a previously known molecule called thioredoxin-interacting protein (TXNIP) is intimately involved with inflammation that can result in the death of the beta cells in the pancreas--the cells that produce insulin. Senior author of the study, Feroz Papa, MD, PhD, associate professor of medicine at UCSF, noted in Science Codex that this molecule "takes stress and makes it worse."

This new study is important because it highlights a substance--TXNIP--whose actions scientists can try to halt, which would then in turn prevent or hinder the inflammation process. Hopefully this approach could be attempted early in the development of diabetes and prevent the disease.

Beta cells and stress
Let's return to the beta cells, which make and secrete the all-necessary insulin. Each beta cell (like all cells) has a structure (organelle, or "little organ") called the endoplasmic reticulum, which serves as a processing center for the cell. The product processed in beta cells is insulin.

When the endoplasmic reticuli in beta cells are stressed, a protein called interleukin-1 (IL-1) initiates inflammation, which in turn leads to the destruction of beta cells. In some people the destruction goes too far, and diabetes develops.

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Targeting the stress
The UCSF researchers found that a protein called IRE1 prompts TXNIP, which then progresses to the production of IL-1 and thus inflammation. Therefore, they proposed if you target TXNIP and eliminate it from the process, you should be able to protect the beta cells and thus maintain insulin production.

An indication that this concept is viable was seen when researchers bred mice without the protein with mice susceptible to developing diabetes. The offspring of these mice did not develop diabetes because their beta cells were protected.

In another recent study, investigators at the University of Sao Paulo Medical School studied the relationship between nine different forms (polymorphisms) of TXNIP, diabetes, and hypertension among Brazilians. They discovered that specific forms of TXNIP were significantly associated with diabetes.

This finding is important because it shows that individuals who carry certain TXNIP genetic variations are more susceptible to developing diabetes and hypertension, a common condition among diabetics. The authors noted that their findings "suggest that genetic variation in the TXNIP gene may act as a 'common ground' modulator of both traits: diabetes and hypertension."

The Brazilian study, the results of the UCSF research, and dozens of other studies on TXNIP point to an important role for this protein in stress and diabetes. Specifically, results of the UCSF study suggest that inhibiting the protein TXNIP may protect beta cells in individuals, according to Papa, which in turn could delay the onset of diabetes.

SOURCES:
Ferreira NE et al. Thioredoxin interacting protein genetic variation is associated with diabetes and hypertension in the Brazilian general population. Atherosclerosis 2012 Mar; 221(1): 131-36
Lerner AG et al. IRE1a induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metabolism 2012 Aug 8; 16(2): 250-64
Diabetes and stress: a central molecule is uncovered. Science Codex

Image: Wikimedia Commons

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