Pathway That can Prevent Type 1 Diabetes Discovered

by Medindia Content Team on Nov 28 2007 3:09 PM

An Indian researcher and his team at UC Davis Health System has discovered a pathway that results in increased inflammation of blood vessels in patients with type 1 diabetes.

According to researchers, their findings suggest that, with good diabetes control, this inflammation may be reduced, possibly resulting in a reduction of heart disease as well.

In the study, Ishwarlal Jialal, director of the Laboratory for Atherosclerosis and Metabolic Research, professor of internal medicine at UC Davis, and his research team has provided the first-ever demonstration of increased expression and signalling in type 1 diabetics of two key receptors within the body’s innate immune system.

Called TLR2 and TLR4, they are part of a family of pattern recognition receptors known as Toll-like receptors (TLRs), so-called because of their similarities to the well-defined Toll gene found in much-studied fruit flies.

Type 1 diabetes is a pro-inflammatory state associated with increased cardiovascular mortality. Inflammation plays a pivotal role in all stages of atherosclerosis, the progressive narrowing and hardening of the arteries over time.

The study found that TLR2 and TLR4 expression and signaling are increased in type 1 diabetes patients and contribute to the pro-inflammatory state.

“It is not unreasonable to speculate that TLR2 and TLR4 promote atherogenesis by contributing to the pro-inflammatory state in type 1 diabetes,” Jialal said.

“Inflammation is central to heart disease, playing a pivotal role in plaque formation and stroke. We may well find that a serendipitous byproduct of controlling diabetes is the simultaneous control of this new pathway, leading to less inflammation and lower risk of heart problems,” he added.

The study represents the first-ever demonstration of increased TLR2 and TLR4 activity in type 1 diabetes monocytes, which are part of the body’s immune system, protecting against blood-borne pathogens by moving quickly to sites of infection.

The immune system comprises the cells and mechanisms that defend the host from infection by other organisms, accomplishing its defense with the help of such pattern-recognition receptors as TLRs for early detection of specific classes of pathogens.

“This finding provides us with a totally new insight into the causes of inflammation in diabetics. It’s an exciting development in the emerging area of TLR research that has potentially wide-ranging implications,” Jialal said.

The study is available both in the online edition of the Journal of Clinical Endocrinology & Metabolism as well on the National Institutes of Health’s PubMed.