Tuesday, July 21, 2009
How Can Eating Excess Protein Raise Blood Glucose?
It is almost an article of faith among low-carbers that the low-carb lifestyle is able to lower blood glucose values in diabetics and pre-diabetics. It would be logical to assume that the lower the carbohydrate intake, the lower the corresponding blood glucose. But recent observations in a limited sample of people who were doing something very close to zero-carbing suggest that this is not necessarily the case.
Donald K. Layman has done some interesting work on the effect of dietary protein on glycemic control that may help explain this phenomenon. In an article in The Journal of Nutrition, he presents a diagram of the glucose-alanine cycle, which appears in modified form above.
For those who are not familiar with this type of diagram, here is a brief explanation. Ingested protein enters the gut and is digested into amino acids. The amino acids are taken up in the blood and proceed to the liver, where many of them are metabolized. However the branched-chain amino acids leucine, isoleucine and valine are unique. Although they constitute 15-25% of protein intake, they experience very little metabolism in the liver. Most of the branched-chain amino acids, abbreviated BCAA, continue to move through the circulation and are eventually absorbed by muscle cells.
In muscle cells the branched-chain amino acids have two possible fates. First, when branched-chain amino acids enter a muscle cell, they promote protein synthesis. Our muscle tissue is continually undergoing repair, and because of this each of us has an individual daily protein need. If sufficient high-quality protein is consumed, this repair is able to take place without loss of lean muscle tissue.
Second, if there is an excess of amino acids in the muscle cells, the surplus branched-chain amino acids enter the pathway of energy production. In order to do this, they must have their amino group (NH3)removed in a process called transamination. The amino group from a BCAA is transferred to a molecule called alpha-keto-glutarate to form the amino acid glutamate. Next, another transamination transfers the amino group from the glutamate to pyruvate, transforming the pyruvate into the amino acid alanine. The alanine leaves the muscle cell and travels to the liver, where it is turned into pyruvate by removal of the amino group, and then the pyruvate is turned into glucose by gluconeogenesis. The liver sends the newly-synthesized glucose into the blood, where it can be taken up by muscle cells and broken down once again into pyruvate. Each pyruvate is ready to accept another amino group from one of the branched-chain amino acids, and the cycle repeats itself until the branched-chain amino acids have been used up.
The glucose-alanine cycle explains why it is possible to have an elevated blood glucose while eating essentially only meat and fat. Normally, leucine signals the muscle cells to synthesize protein and maintain lean body mass. When an excess of branched-chain amino acids is available, leucine serves as a metabolic signal to muscle cells telling them to upregulate their use of BCAA as a fuel, while simultaneously downregulating their use of glucose as a fuel. Any glucose that appears in the cell is preferentially broken down into pyruvate, which is used to accept excess amino acid nitrogen (NH3 groups) and allow them to be removed them from the cell in the form of alanine. In the liver, the alanine is recycled into glucose, and the glucose is returned to the blood until it is no longer needed to mop up excess NH3 groups in peripheral tissues.
If this pathway is correct, it shows that excess amino acids not only provide the raw materials for glucose synthesis in the liver, but they also require additional glucose synthesis in the liver in order to allow branched-chain amino acids to be converted into energy.
Metabolic regulation is a huge topic, and this post presents only a small piece of it. Once again, please do not modify your lifestyle in accordance with what you read here. In the overall context of a human organism, it may be incomplete or even incorrect. However the glucose-alanine cycle does provide a possible explanation for what some people have seen with regard to a higher-than-normal blood sugar while eating essentially zero carbohydrates.