How the body decreases blood glucose concentrations after eating

Whilst this course has been primarily created for healthcare professionals to help reduce concerns around prescribing and managing insulin, we hope that it is of interest to people with diabetes who do not have regular access to a healthcare professional and who want to find out more about how insulin works.

With this in mind, in this article, as in others throughout the course, there is a brief section at the top called ‘Essential knowledge’ that summarises the key things that you need to know.

The next section ‘In greater depth’ goes into a bit more detail and expands on the explanation (this is aimed at healthcare professionals but may be too technical in nature for some of you). Please don’t let that put you off continuing with the course!

Essential knowledge

How is glucose produced? Glucose is produced by breaking down carbohydrates, principally in the small intestine, when we eat a meal containing carbohydrates (such as pasta or bread).

This glucose enters the bloodstream. When fasting our blood glucose is normally about 4.5-5.5 mmol/L but this can rise to 7 mmol/L or above when eating, yet it returns to normal within 2 hours of eating.

How does our body manage this? Glucose cannot cross cell membranes without using transport proteins and insulin is required to facilitate the removal of glucose from the blood stream so that it enters cells.

When glucose is in excess, the body stores it away in the form of glycogen in a process stimulated by insulin. Glycogen is a large highly branched structure, made from lots of glucose molecules linked together. When required, glycogen can be easily and rapidly broken down again to form glucose.

Glycogen is mainly stored in the liver (where it makes up as much as 10% of liver weight and can be released back into the blood stream) and muscle (where it can be converted back to glucose but only used by the muscle). Therefore, excess glucose is removed from the blood stream and stored.

In greater depth

Glucose uptake by tissues

Glucose cannot cross cell membranes without using transport proteins. We will mainly consider the glucose transporter protein GLUT 4. Have a look at the diagrams below. In the left hand diagram, there is no insulin present so Glut 4 remains inside the cell and glucose is taken up from the bloodstream in low amounts using Glut 1 or 3. In the right hand diagram, insulin signals to the cell to translocate Glut 4 to the cell membrane. Now large amounts of glucose can be taken into the cell, via the Glut 4 transporters, as well as low levels through Glut 1 or 3. Insulin is key to the process.

_{Figure: insulin stimulates Glut 4 translocation to the membrane}

GLUT 1 and 3 provide basal glucose uptake, meaning the cell always has the capability to take up low levels of glucose. However, GLUT 4 is insulin-sensitive (muscle or adipose cells). This means that when we eat, glucose upregulates insulin, and insulin binding to the insulin receptor results in the movement of GLUT 4 from intracellular granules to the cell membrane, enabling uptake of large amounts of glucose by cells. Therefore, glucose is removed from the blood stream and enters cells.

_{Figure: glucose storage as glycogen}

Glucose storage as glycogen

When glucose is in excess, the body stores it away in the form of glycogen in a process stimulated by insulin. Glycogen is a large highly branched structure, made from lots of glucose molecules linked together. When required, glycogen can be easily and rapidly broken down again to form glucose.

Glycogen is mainly stored in the liver (where it makes up as much as 10% of liver weight and can be released back into the blood stream) and muscle (where it can be converted back to glucose but only used by the muscle). Therefore, excess glucose is removed from the blood stream and stored.

_{Figure: metabolism of glucose to make ATP by glycolysis (breakdown of carbohydrates to the precursors entering the Krebs Cycle) and the Krebs Cycle diagram}

Metabolism of glucose to make ATP by glycolysis and the Krebs Cycle

Glucose enters cells where it undergoes phosphorylation to form glucose-6-phosphate. Changing the form that the glucose is in means that glucose cannot be transported back outside the cell, and the cells sense that the concentration of glucose is higher outside the cell than inside. Therefore they keep transporting glucose into the cells, resulting in a reduction in glucose concentrations in the bloodstream.

Once inside the cell cytoplasm, glucose enters the glycolysis pathway. This is a multi-step pathway that results in the generation of 2 ATP, and is controlled in part by insulin and glucagon. ATP generation is very important for the body, as this is the main energy currency for cells.

The end product of the glycolysis pathway is acetyl coA. This molecule can then enter the Krebs Cycle in the mitochondria which produces 36 ATP, making it the power generator of the cell in most circumstances. Therefore, the body metabolises glucose to generate energy.