Natural molecule could help insulin inefficiency in type 1 diabetes

by Barbara Hewitt on November 15, 2013

New research has found a disease mechanism in type 1 diabetes that can be targeted using simple, naturally occurring molecules to help prevent the disease.

The work, led by Harvard School of Public Health (HSPH) in the United States, highlights a previously unrecognised molecular pathway that contributes to the malfunction of insulin producing pancreatic beta cells in humans and in mice with type 1 diabetes.


The new study breaks new ground because it focuses on boosting beta cell performance and shows that beta cell preservation is possible

The researchers say that it shows that a chemical intervention can help beta cells function properly and survive. Currently, there is no prevention or cure for type 1 diabetes and the only treatment is insulin therapy by injection or pump.

In type 1 diabetes, the beta cells are mistakenly attacked by the body’s own immune system, and prior research has focused on ways to prevent this autoimmune response. However, this study breaks new ground because it focuses on boosting beta cell performance and shows that beta cell preservation is possible even in the face of such immune attack.

Using human pancreatic samples and mouse models, the HSPH researchers, with colleagues from Harvard Medical School, the Broad Institute of Harvard and MIT, and the University Libre in Brussels, sought to tease apart the mechanisms of beta cell failure in type 1 diabetes.

They homed in on the function of the endoplasmic reticulum (ER,) a mini organ inside cells where proteins and lipids are processed and packaged and undergo quality control before they reach their destinations in the body. The ER is known to play a critical role in supporting the work of beta cells.

The researchers found that, in animal models and in humans with type 1 diabetes the ER function is compromised by the immune attack. This reduced ER function results in ER stress and contributes to the death of beta cells and the insulin insufficiency that is characteristic of type 1 diabetes.

In earlier studies, researchers in the Hotamisligil lab showed that ER stress in other tissues plays a key role in obesity and type 2 diabetes, and can be corrected with so called chemical chaperones such as tauroursodeoxycholic acid (TUDCA,) a bile acid.

Based on that previous research, the scientists applied TUDCA to mouse models. They found that ER function improved both in mice with diabetes and those with pre-diabetes. Beta cells functioned better and were less likely to die, and, to the researchers’ surprise, the treated mice had a dramatically reduced incidence of type 1 diabetes. The researchers also identified the specific molecular pathway through which TUDCA influences ER function.

‘The study is exciting because it suggests that improving ER function before the onset of disease could reduce T1D incidence’ said lead author Feyza Engin, research associate in the HSPH Department of Genetics and Complex Diseases.

Advances in medicine now allow physicians to identify, with great accuracy, those with very high risk for developing type 1 diabetes. ‘There is really a need for some safe and mild interventions that can prevent emergence of type 1 diabetes in these populations,’ said Gokhan Hotamisligil, chair of the department of genetics and complex diseases at HDPH.

‘TUDCA is safe and inexpensive. It’s possible that TUDCA or another molecule that acts via the described mechanisms could be used as a novel therapeutic approach to keep those at risk for type 1 diabetes disease free for long periods of time, or could even prevent the disease all together,’ he added.

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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