Two Proteins May Offer New Light on Treating Diabetes

As the long struggle to fully understand and treat diabetes goes on, researchers have revealed another paradox in the way the disease functions.  The conflicting influences involved in obesity have thrown up a chemical behavior that could provide another lead for scientists hoping to improve treatment for this increasingly widespread health problem.

Blood sugar levels rise when a person has eaten something, especially sugary or carbohydrate-rich foods.  In a healthy person, the beta cells in the pancreas then release the hormone insulin, which acts as a messenger, telling the body’s cells to take up the sugar from the blood and store it for their own energy needs.  Diabetes Type II occurs when the tissues have become unable to respond to this message, and the blood sugar therefore remains high, which can cause damage to the whole system.


With some 25.8 million Americans now diagnosed as diabetic and another 79 million pre-diabetic, with possibly another seven million undiagnosed, the need to find treatment that is more effective or even a cure becomes ever more urgent.  The risk of developing Type II diabetes is known to be increased by several factors, including obesity, age, poor diet involving high levels of fat and sugar, low exercise levels, and some genetic factors.  Obesity is believed to be one of the most important, and with America’s high levels of obesity, diabetes is an increasing source of concern as time passes.

Now researchers at the prestigious research facility at Boston’s Children’s Hospital have discovered that cellular inflammation once held to be a contributing factor in the development of diabetes actually releases two proteins that help maintain good blood sugar levels.

Dr. Umut Ozcan and his team previously demonstrated that obesity causes stress to a cellular structure called the endoplasmic reticulum, which handles proteins within the cell.  For the past 20 years, this stress was believed to be a factor in causing insulin resistance, one of the first symptoms of diabetes.  It is a key link between obesity and Type II diabetes.

However, using obese and diabetic mice, Dr. Ozcan and his colleagues have discovered that the inflammation causes two proteins to be activated which are actually vital for maintaining steady blood sugar levels.  The first protein, XBP1s, is released in response to the cellular stress in order to relieve it, and the team found this protein could not function in obese mice.  However, a second protein called p38MAPK, also released in response to the cellular stress, alters the composition of the first protein, increasing its efficiency so that it can control blood sugar levels.

The scientists also found levels of the second protein were reduced in the obese, diabetic mice, but that artificially increasing its level in their livers reduced insulin resistance, reduced their blood sugar levels, and reduced their cellular inflammation.

The study, published in the Nature Medicine journal, suggests that boosting one or both of these two proteins could be a new route for research into treatment options for diabetes.  In addition, it throws new light on the way in which obesity affects the body’s ability to respond to cellular stress and deal with blood sugar levels.  However, Dr Ozcan said it also suggested the use of p38MAPK inhibitors could be problematic in treating inflammatory diseases such as asthma, psoriasis and Crohn’s Disease.

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