Insulin promotes Glucose metabolism

Insulin Promotes Liver Uptake, Storage, and
Use of Glucose
One of the most important of all the effects of insulin is to cause most of the glucose absorbed after a meal
to be stored almost immediately in the liver in the form of glycogen. Then, between meals, when food is
not available and the blood glucose concentration begins to fall, insulin secretion decreases rapidly and
the liver glycogen is split back into glucose, which is released back into the blood to keep the glucose concentration from falling too low.

The mechanism by which insulin causes glucose uptake and storage in the liver includes several almost
simultaneous steps:
1. Insulin inactivates liver phosphorylase,the principal enzyme that causes liver glycogen to
split into glucose. This prevents breakdown of the glycogen that has been stored in the liver cells.

2. Insulin causes enhanced uptake of glucose from the blood by the liver cells. It does this by
increasing the activity of the enzyme glucokinase, which is one of the enzymes that causes the initial
phosphorylation of glucose after it diffuses into the liver cells. Once phosphorylated, the glucose is
temporarily trapped inside the liver cells because phosphorylated glucose cannot diffuse back
through the cell membrane.

3. Insulin also increases the activities of the enzymes that promote glycogen synthesis, including
especially glycogen synthase, which is responsible for polymerization of the monosaccharide units to
form the glycogen molecules.

The net effect of all these actions is to increase the amount of glycogen in the liver. The glycogen can
increase to a total of about 5 to 6 per cent of the liver mass,which is equivalent to almost 100 grams of stored glycogen in the whole liver.

Glucose Is Released from the Liver Between Meals.

When the blood glucose level begins to fall to a low level between meals, several events transpire that cause the liver to release glucose back into the circulating blood:

1. The decreasing blood glucose causes the pancreas to decrease its insulin secretion.

2. The lack of insulin then reverses all the effects listed earlier for glycogen storage, essentially stopping further synthesis of glycogen in the liver and preventing further uptake of glucose by the liver from the blood.

3. The lack of insulin (along with increase of glucagon, which is discussed later) activates the enzyme phosphorylase, which causes the splitting of glycogen into glucose phosphate.

4. The enzyme glucose phosphatase, which had been inhibited by insulin, now becomes activated by the
insulin lack and causes the phosphate radical to split away from the glucose; this allows the free glucose to diffuse back into the blood.

Thus, the liver removes glucose from the blood when it is present in excess after a meal and returns it to the blood when the blood glucose concentration falls between meals. Ordinarily, about 60 per cent of
the glucose in the meal is stored in this way in the liver and then returned later.

Insulin Promotes Conversion of Excess Glucose into Fatty Acids and Inhibits Gluconeogenesis in the Liver.

When the quantity of glucose entering the liver cells is more than can be stored as glycogen or can be used for local hepatocyte metabolism, insulin promotes the conversion of all this excess glucose into fatty acids.

These fatty acids are subsequently packaged as triglycerides in very-low-density lipoproteins and transported in this form by way of the blood to the adipose tissue and deposited as fat.

Insulin also  inhibits gluconeogenesis. It does this mainly by decreasing the quantities and activities of the liver enzymes required for gluconeogenesis.

However, part of the effect is caused by an action of insulin that decreases the release of amino acids
from muscle and other extrahepatic tissues and in turn the availability of these necessary precursors
required for gluconeogenesis. This is discussed further in relation to the effect of insulin on protein
metabolism.

 References:
© Copyright Guyton and Hall Textbook of Medical Physiology