Absorptive & post-absorptive states ◦ Absorptive state ◦ Post-absorptive state ◦ Metabolism

Overview

Insulin doesn’t simply control blood sugar. Although insulin release from β-cells of the pancreas is triggered by elevated blood glucose - typically after a meal - the effects of insulin profoundly change the way the body metabolises not only carbohydrates like glucose, but also fats and proteins. From a metabolic point of view, the body can be viewed as having two states. In the first – promoted by insulin – glucose is used to fuel the body, is available in excess and is stored to maintain a fixed blood glucose level. In the second – activated by low insulin levels, the body relies on stores to produce enough glucose to keep the central nervous system active, while other tissues depend on other sources of fuels (ketones and fatty acids). There are other systems that control whole body metabolism, but none has the far-reaching effects that insulin has.

Absorptive and post-absorptive states

The body has two basic metabolic states, absorptive (during the approximately four hours it takes to digest a meal and store energy) and post-absorptive (when the body uses fuels stored during the absorptive phase). In most cultures, the human body is in the post-absorptive state for short periods between meals and during the night. In each state the body is using different fuel supplies to produce energy, and insulin - as the most important hormone governing the metabolic state of the body – is the master switch that changes all of the body’s "metabolic settings" appropriately:

High insulin/Absorptive state

Let’s consider the effects that insulin has, when it is released after feeding as blood glucose levels start to rise as sugars are absorbed from the gastrointestinal tract. In order to keep blood glucose levels steady, this surge of available energy needs to be packed away (anabolism) in big molecules (e.g. glycogen and triglycerides) from which it can be released later. Meanwhile all the tissues of the body utilise glucose as the main fuel source, while it is in abundance. At the same time, fats and proteins are absorbed from the gut and these can be transformed into triglycerides and protein for catabolism at a later stage too. All of this is driven by increased levels of insulin, binding to insulin receptors on various cells.

Glucose uptake & utilisation
All tissues take up glucose and use it as an energy source.
Some (see below) store excess as glycogen or triglyceride.

Amino acid uptake
Liver converts amino acids to energy via α-ketoacids or urea as waste.
Other tissues make proteins out of them.

Glycogen synthesis
Storage of excess glucose as glycogen in muscle and liver.
Adipocytes and the liver both use two pathways:

• Convert glucose to glycerol-3-phosphate then to triglycerides
• Convert glucose to fatty acids, then to triglycerides

Adipocytes will also take up circulating fatty acids to convert to triglycerides for storage. Most of the triglycerides produced by the liver are packaged as VLDL and enter the circulation. Lipoprotein lipase on endothelial cells in adipose tissue frees up the triglyceride component by cleaving them into monoglycerides and fatty acids, the latter of which is taken up into adipocytes.

Low insulin/Post-absorptive state

As glucose levels from the GI tract start to fall, so does the concentration of insulin in blood. In this post-absorptive state, there is the risk of blood glucose falling too low. These setting aim to keep blood glucose up for the nervous system, which is dependent on aerobic metabolism. Glucose uptake is switched off in many tissues by down-regulation of cell membrane glucose transporters. Most tissues start to burn fatty acids (excluding the nervous system) and ketones (including nervous system) as sources of fuel.

Protein catabolism/Amino acid release
All tissues convert proteins to amino acids and release them into the blood.
Liver converts amino acids to urea or glucose (via α-ketoacids as above; this is gluconeogenesis).

Glycogen catabolism (activates glucose release from liver)
Muscle: Catabolises glycogen to lactate and pyruvate and releases them.
Liver: Catabolises glycogen (glycogenolysis) and converts glycerol/lactate to glucose (gluconeogenesis).

Ketone synthesis & release
Liver converts fatty acids to ketones or burns them as fuel.
Ketones used by all tissues (including the nervous system as fuel).

Triglyceride catabolism (activates fatty acid and glycerol release from adipocytes)
Adipose tissue catabolises triglycerides to glycerol and fatty acids. These are converted to glucose by the liver (gluconeogenesis).

Metabolism of carbohydrates, proteins and fats

We can draw all of the mechanisms described above to show how the body changes the way it metabolises carbohydrates, fats and proteins in one diagram. It is quite daunting to look at the totality of pathways in one go, so let’s start with just the absorptive state first:

Start at the gastrointestinal tract (GI): by the time digestion has done its work on food, the body absorbs simple carbohydrates like glucose, the amino acids that result from protein breakdown and triglycerides are packaged into chylomicrons. Circulating chylomicrons are subsequently broken down to release fatty acids by lipoprotein lipase on endothelial cells in adipose tissue. Glucose is taken up by all three major tissues: the musculature, adipose tissue and the liver. All cells take up amino acids for protein synthesis, but the liver can also use any excess to store energy as triglycerides (see below).

In the liver, glucose is converted into glycogen or triglycerides. Triglycerides are composed of glycerol-3-phosphate and fatty acids, both of which can be formed from glucose. Most of the triglycerides produced by the liver are released into the circulation as very low density lipoproteins, which are converted back to fatty acids and monoglycerides by the enzyme lipoprotein lipase, located on endothelial cells within adipose tissue. Fatty acids are then taken up by adipocytes and converted back to triglycerides by the addition of glycerol-3-phosphate.

Absorbed amino acids not used in protein synthesis are taken up by the liver and converted to either urea (to be disposed of by the kidneys) or triglycerides by a slightly convoluted process involving the stepwise production of a-ketoacids, conversion to fatty acids and packaging into triglycerides with glycerol-3-phosphate.

In this way, energy is stored in the form of glycogen by the liver and musculature and as triglycerides by adipose tissue. To complete the picture, we need to depict how these stores are released when insulin levels subside during the post-absorptive state of metabolism. It’s not easy to depict all of this on a single diagram, but it can be done (though inelegantly):

In the post-absorptive state, muscles catabolise stored glycogen into pyruvate and lactate, which are then released into the circulation. The liver converts both glycogen and pyruvate into glucose and releases it into the blood (this is one kind of gluconeogenesis). Adipose tissue catabolises triglycerides into fatty acids and glycerol. The liver converts glycerol into glucose (more gluconeogenesis), while the fatty acids are transformed into ketones – an alternative fuel source that all tissues can use. Any fatty acids not converted by the liver into ketones are also used as fuel, although the nervous system does not utilise it. Finally, any proteins that are non-essential can be broken down into amino acids, which are converted (again) by the liver into α-ketoacids and subsequently into glucose.