Low calorie diet can reverse type 2 diabetes

Diabetes goes into remission in many patients who undergo bariatric weight-loss surgery, which significantly restricts caloric intake prior to clinically significant weight loss.The research team investigated the effects of a very low calorie diet VLCD, consisting of one-quarter the normal intake, on a rodent model of type 2 diabetes.

Using a novel stable (naturally occurring) isotope approach, which they developed, the researchers tracked and calculated a number of metabolic processes that contribute to the increased glucose production by the liver. The method, known as PINTA, allowed the investigators to perform a comprehensive set of analyses of key metabolic fluxes within the liver that might contribute to insulin resistance and increased rates of glucose production by the liver-two key processes that cause increased blood-sugar concentrations in diabetes.

Using this approach, the researchers pinpointed three major mechanisms responsible for the VLCD's dramatic effect of rapidly lowering blood glucose concentrations in the diabetic animals. In the liver, the VLCD lowers glucose production by: decreasing the conversion of lactate and amino acids into glucose; decreasing the rate of liver glycogen conversion to glucose; and decreasing fat content, which in turn improves the liver's response to insulin.

These positive effects of the VLCD were observed in three days. Using this approach to comprehensively interrogate liver carbohydrate and fat metabolism, we showed that it is a combination of three mechanisms that is responsible for the rapid reversal of hyperglycemia following a very low calorie diet.
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How protein breakdown causes leukemias and brain cancer

An enzyme that is responsible for the breakdown of specific amino acids in food plays a key role in the development of leukemias and brain cancer. The researchers have discovered a surprising link between energy metabolism and the epigenetic code. These labels in the DNA of cancer stem cells determine the activity of genes and many cellular functions.

Acute myeloid leukemia AML is an aggressive type of blood cancer that often relapses in the wake of successful initial treatment. Stem cells that are resistant to therapy are believed to be responsible. Reseachers examined patient samples by comparing the composition of proteins of AML stem cells and leukemia cells without stem cells properties.

The investigators found suspiciously high levels of an enzyme called BCAT1 in the stem cells. These levels rose even higher during a cancer recurrence. The researchers considered this to be a clue that BCAT1 might be linked to therapy resistance. Cancer researchers have suspected for some time that the BCAT1 enzyme, which is responsible for the breakdown of specific proteins in food, plays a role in the development of malignant tumors.

 They discovered that an overproduction of BCAT1 increases the aggressiveness of malignant brain tumors and breast cancer. BCAT1 reduces the levels of this key molecule and this leads to increased levels of chemical labels in the DNA. The tiny methyl groups that are attached to DNA determine whether particular genes are active or silent and, thus, have an immense impact on all cellular functions.

They increase cancer-promoting methylation of DNA. AML is known for an extremely heterogeneous pattern of genetic alterations. However, misregulated methylation with its drastic consequences for the whole cell appears to be a common characteristic of this malignant disease.

The finding that BCAT1 drives cancer-promoting methylation in AML stem cells and other cancer stem cells opens up new options for therapy. A blockade of the enzyme using a targeted agent might normalize DNA methylation and thereby reduce cancer spread and therapy resistance.
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Activation of immune T cells changes behavior

Researchers have discovered that T cells immune cells that protect the body from infections and cancer change the body's metabolism when they are activated, and that this activation leads to changes in behavior.

It is currently known that individual T cells change their metabolism to meet their energy needs after being activated, but the systemic metabolic effect of sustained activation of the immune system has remained unexplored.

 To understand the systemic effects, the group looked at T cell activation in mice designed to lack a surface receptor called PD-1, which is necessary for inhibiting the activity of T cells. T cells remain activated in mice without the receptor, similar to those in the immune systems of people with certain types of autoimmune disease.

In these mice, they found that amino acids molecules that are used to build proteins were depleted in the blood, and that they were increased in the T cells themselves, implicating the T cells in the change. The team tracked and imaged amino acids in many organs, and found that the depletion of amino acids from the blood was taking place due to the accumulation of amino acids in activated T cells in the lymph nodes, showing that strong or long lasting immune responses can cause metabolic changes elsewhere in the body.

Researchers analyzed the biochemistry of the brain, they found that the systemic decrease in the amino acids tryptophan and tyrosine in blood led to lower amounts available in the brain, limiting production of the neurotransmitters serotonin and dopamine. These neurotransmitters affect emotions, motivation and fear.

Serotonin is often a target of drugs that combat depression. The researchers found that their depletion in mice without PD-1 resulted in behavioral changes dominated by anxiety and exacerbated fear responses, which could be remedied by providing a diet rich in an essential amino acid.
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Impacts of proteins on immune system

Different genetic make-up can impact on the activity of the immune system and our ability to fight cancer.

Proteins are made up of thousands of smaller units called amino acids, which are attached to one another in long chains.

Proteins do most of the work in cells and are required for the structure, function, and regulation of the body's tissues and organs.

 A protein called ULBP6 leads to the removal of damaged cells. There are two types of this protein found in different people.

The ULBP6 protein is found on the surface of damaged cells, including several types of cancer cells, and acts as a signal to white cells in our immune system that the damaged cell should be killed.

There are two major types of protein in the population and people who inherit a certain subtype have been shown to have a poor outcome after stem cell transplantation, a procedure used to treat leukemia, which is commonly referred to as bone marrow treatment.

The two types of ULBP6 differ only by two amino acids out of a total of around 180 and it has important influence on patient outcomes. One form of ULBP6
 forms a very strong bond indeed with its receptor NKG2D on the immune system.

This shows why transplants work less well in some people, which is an important step on the path to developing better transplant therapy for more people living with blood cancer.

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Amino acids that starve cancer

Researchers at the cancer research UK discovered that remoing serine and glycine from the diet of mice reduced the growth of lymphoma and intestinal cancer.

Dr Oliver M, of University of Glasgow said the discovery dictate removing of the two proteins through a controlled diet plan will be part of treatment for some cancer patients.

Professor Karen Vousden, Cancer Research UK's chief scientist said the protein restriction should be for a short period of time and must be controlled by doctors for safety of cancer patients.

Amino acids are very important for making proteins, healthy cells can make serine and glycine. Cancer cells depend on these amino acids from the food we eat.

Science communication manager at cancer research UK, Dr Emma Smith said cutting off the nutrients necessary for cancer growth and division to prevent tumors is interesting.