Decades old mystery solved as researchers map the effect of T2 diabetes on the lymphatic vessels.


Approximately 28 million Americans live with Type 2 diabetes, a condition characterized by high blood sugar levels.  The immune system plays a part in type 2 diabetes. Researchers have linked insulin resistance to high levels of cytokines, which are released in response to inflammation in the body.  The immune system’s response to inflammation leads to fat cells being unable to respond well to insulin and sees the fat cells releasing fatty acids into the blood, leading to higher than normal levels of cholesterol.  It has long been known that if the patient has diabetes, is at risk of diabetes, or has a family history of diabetes one of the first symptoms to show is enlargement of lymph nodes, the lymphatic system is a major part of the immune system.

However, there is still much that is unknown as to how diabetes effects the body’s lymphatic vessels. Now, a study from University of Missouri researchers has identified for the first time how the condition affects lymphatic vessels, a breakthrough that could lay the groundwork for new therapies to improve the lives of people with Type 2 diabetes.  The opensource study is published in the journal Cardiovascular Research.

Previous studies show that the lymphatic system’s primary role is to transport lymph, a clear fluid that contains white blood cells that help rid the body of antigens, to lymph nodes where immune responses are activated. The current study shows for the first time that when individuals have Type 2 diabetes, the walls of their lymphatic vessels are defective and become increasingly permeable, or leaky.

The team likens the permeability of a healthy lymphatic vessel to a porous garden hose, which is designed to allow water to escape through small holes in the hose. However, they explain that a lymphatic vessel in a person with Type 2 diabetes is like a porous garden hose that has been drilled with large holes, letting too much water escape. The results show that when the lymphatic vessel is too permeable, lymph and antigens are not transported to the lymph nodes.

Studying lymphatic vessel function in animals has been a challenge for researchers, because unlike blood vessels, lymph vessels are clear and appear almost invisible. However, the researchers developed a new investigative method to measure lymphatic vessel permeability and found that the vessels in Type 2 diabetes produced nitric oxide levels much lower than healthy lymphatic vessels.

The results showed that when an individual has Type 2 diabetes, cells in the lymphatic vessels aren’t producing enough nitric oxide, which is essential to maintaining the integrity of their endothelial layer so that they function properly. The researchers found that by giving the lymphatic vessels L-arginine, an amino acid commonly found in red meat, poultry, dairy products and nutritional supplements, they were able to boost their nitric oxide production and restore their ability to act as a barrier.

While more studies are needed, the lab  is hopeful the findings could lead to further research for developing new treatments or therapies for individuals with Type 2 diabetes.

Source:  University of Missouri

 

Lymphatic vascular integrity is disrupted in leptin receptor-deficient (db/db) mice. Diabetic db/db mice were obese.  (D) and db/db (E) vessel. Under epifluorescence, fluorescent albumin leakage from the WT vessel is not visible (F), but it is seen extravasating from the db/db vessel (G). Permeability values for the WT (D and F) and db/db (E and G) collecting lymphatic vessels were 1.1 and 595 × 10−7 cm/s, respectively. Both vessels contained a single valve that was normal in appearance and functional (i.e. remained closed in response to an adverse pressure gradient of 2 cm H2O). Evans Blue dye lymphangiography was performed on WT and db/db mouse hindlimbs (H and I) and demonstrates a lymphatic leakage phenotype is present in vivo in the popliteal collecting lymphatics (n = 3). Fluorescence images were both taken at the same time point. Scale bar is 100 μm in D and F and 200 μm in E and G.  Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling.  Scallan et al 2015.

Lymphatic vascular integrity is disrupted in leptin receptor-deficient (db/db) mice. Diabetic db/db mice were obese. (D) and db/db (E) vessel. Under epifluorescence, fluorescent albumin leakage from the WT vessel is not visible (F), but it is seen extravasating from the db/db vessel (G). Permeability values for the WT (D and F) and db/db (E and G) collecting lymphatic vessels were 1.1 and 595 × 10−7 cm/s, respectively. Both vessels contained a single valve that was normal in appearance and functional (i.e. remained closed in response to an adverse pressure gradient of 2 cm H2O). Evans Blue dye lymphangiography was performed on WT and db/db mouse hindlimbs (H and I) and demonstrates a lymphatic leakage phenotype is present in vivo in the popliteal collecting lymphatics (n = 3). Fluorescence images were both taken at the same time point. Scale bar is 100 μm in D and F and 200 μm in E and G. Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling. Scallan et al 2015.

 

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