The Portal Problem


This morning several million people have taken a shot of insulin to control their blood sugar levels, as they did yesterday, and as they will do tomorrow. The insulin is delivered into the fatty tissue of the abdomen and is slowly absorbed into the blood stream. This method of taking insulin differs in a very important way from the means by which the pancreas supplies insulin to the body and this is the source of much trouble.

Insulin courses through the blood and so we need to think for a moment about the path that blood takes as it nourishes the body. Normally, blood is pumped from the left ventricle of the heart through the great arteries which branch and branch until they become tiny arterioles and finally capillaries, where the act of nutrient and gas transfer takes place. Immediately, the blood courses back to the heart – first through veinules which meet and become veins and eventually through the great veins which feed the right atrium. The right ventricle delivers the blood to the lungs and then back to the left side of the heart for delivery back to the tissues of the body. Thus in the normal instance, the blood in a particular capillary bed interacts with one and only one tissue and then returns to the heart.

There are a few exceptions to this organization and one of these involves insulin. Insulin is secreted from beta cells in the islets of Langerhans found in the pancreas. As elsewhere, these pancreatic capillaries join other capillaries to form veinules and eventually a vein. Then something strange happens. Rather than go to the heart, the vein becomes an artery again and delivers the blood to the liver. The blood that had just left the pancreas now is full of hormones derived from the islets and these hormones act first on the liver. Then as before, the capillaries become veinules and veins and eventually the great vein that feeds the right atrium. At this point the hormones from the pancreas mix with blood from throughout the body and then are sent outwards. Before this great mixing, the liver has already received its signal – why?

The liver serves a number of important purposes, two of which will be mentioned here. It serves as a detoxifier of exogenous compounds and it serves as the major source of glucose which supplies the body with energy. For both of these reasons, there has evolved a specialization of the circulatory system that delivers material absorbed from the gut directly to the liver for processing. This specialized bit of blood vessels is called the hepatic portal system (hepatic is a word biologists use to refer to the liver) and includes the output of the pancreatic islets of Langerhans.

The reason why this is relevant to diabetes and insulin therapy is that the concentration of the insulin in the liver is approximately twice what the rest of the body sees. We do not know exactly why this is the case and there is still some debate on the issue, however, most diabetes health care workers believe that things are arranged this way because of the liver’s role in generating glucose.

The liver generates a lot of glucose. The level of glucose in the blood of a fasting individual may be in the range of 70 to 90 grams per deciliter (g/dL). This is all coming from the liver through the process of making new glucose molecules from amino acids (we scientists can’t resist big words so we call it “gluconeogenesis”). When that individual eats a meal the level shoots up to 200 – 300 g/dL. From an engineering standpoint, it would be a good idea to get the liver to shut off production when glucose is coming in from the gut.

Going back to the person with diabetes who has just given himself his morning injection of insulin, that insulin will be seen at an equal concentration throughout the body including the liver. You can now see the problem. The insulin dose has to be large enough to handle the liver yet not so large as to mess up aspects of its regulation of other parts of the body. Patients for whom insulin does not fully control their blood glucose are dealing directly with this issue.

One of the reasons it is a good idea to cut back on the carbs and in general to eat slower is because with diabetes, it is harder to shut down gluconeogenesis. Besides, food tastes good. Slow down and enjoy it.

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