Letzte Aktualisierung am 7. December 2023 von Dr. Michael Zechmann-Khreis
Transport proteins in the intestine
GLUT and SGLT are transport proteins (carrier proteins) that transport certain substances through cell walls. GLUT is the abbreviation for glucose transporter, SGLT is the abbreviation for “sodium-glucose linked transporter“, i.e. “sodium-dependent glucose transporter”. The physiology and the exact functions and tasks of the transport proteins have not yet been fully investigated, i.e. the mechanisms by which the various types of sugar are absorbed into the body are not fully understood. There are heated debates among experts in this regard. The current status is summarized below, but only with regard to its relevance for intestinal fructose intolerance.
Absorption of sugars from the chyme
A cell wall is a barrier that prevents foreign substances from entering the cell. However, since the body must be able to absorb substances and release them again via the cells, there are various mechanisms for transporting these substances through the cell wall. The transport proteins can actively or passively transport substances through the cell wall of the brush border cells (enterocytes). Other factors are often necessary for this. The SGLT-1 transporter, for example, requires the sodium ion Na+. This sodium ion binds to the transporter, causing it to change its shape and only then can the glucose (together with the sodium) be transported through the cell wall. Sodium is, so to speak, a key that unlocks this door for glucose.
Transport proteins are not fixed constants
These transport proteins are not fixed constants. There is therefore no fixed number of precisely defined locations in the small intestinal mucosa. They are produced depending on their necessity, the time of day and age. For example, if there is a lot of fructose in the chyme, the SLC2A5 gene is activated via a specific signaling pathway to form mRNA, which is then translated into GLUT-5. This allows the fructose to be absorbed. The body reacts to the food supplied by starting the corresponding absorption mechanisms. GLUTs are therefore formed depending on the sugar concentration in the food pulp, among other things, and then transport the corresponding sugars into the cells of the small intestine and finally into the blood. They are not permanently anchored in the cell wall, but can translocate, i.e. change their position.
Text explanations: mRNA is the abbreviation for messenger RNA. This is a copy of a gene segment, which is created in the cell nucleus and is derived from the then, through various processes, a protein can be produced.
As described above, the number of GLUT-5 transporters is also dependent on the fructose concentration in the chyme (3). GLUT-5 absorbs the fructose from the food pulp and brings it into the small intestine. From here, the fructose enters the bloodstream via GLUT-2 transporters. However, GLUT-5 is not only formed in dependence on fructose in the chyme, but is also subject to a circadian rhythm (2). In rats, for example, GLUT-5 is produced significantly more at the end of the day than at the beginning of the day (1) and so it is possible that the time of day also plays a role in humans. GLUT-7 can also absorb fructose from food (5), but appears to play a subordinate role in the absorption of fructose. GLUT-2 transports glucose very effectively, but also fructose, mannose or galactose. This transporter is mainly found in liver cells, but also in many other organs, such as the small intestine. Here it is primarily responsible for transporting glucose and fructose out of the small intestine and into the bloodstream. SGLT-1 transports glucose, but not fructose.
Why does glucose help with fructose absorption?
If a lot of glucose is ingested with food, GLUT-2 transporters can migrate (translocate) to the cell wall on the small intestine side or be formed directly on this side of the cell. As these GLUT-2 transporters can also absorb fructose, they relieve the GLUT-5 transporters and help to absorb fructose from the intestine.
How does fructose intolerance develop?
Now the important question arises as to which mechanism is involved in the Fructose intolerance is disturbed. What is the reason for the intestinal Fructose intolerance? Are the GLUT-5 transporters not working properly? Are there too few of these vans? Does the signal transmission work and will therefore produce too little mRNA and consequently too few transporters. educated? Or is fructose absorption disturbed in another way?
We don’t know the answer (yet)! Anything is possible. It is also possible that there are different problems that together cause the clinical picture of intestinal fructose intolerance. So maybe there are 2 or 3 reasons, or maybe a previously unknown mechanism is to blame for the malabsorption of fructose. A great deal of research work is still required here in the coming years.
Sorbitol (E420) blocks GLUT-5?
It is often stated that sorbitol blocks GLUT-5 and should therefore be avoided in cases of intestinal fructose intolerance. Experience shows that sorbitol (and other sugar alcohols) actually has a negative effect on fructose intolerance and fructose absorption. However, scientific evidence, especially for the underlying mechanism, is still lacking. Nevertheless, these sugar alcohols should be avoided.
What we know today
Basics of the “glucose trick”
We know from the processes described above that dextrose (glucose) helps to absorb fructose:
- On the one hand, high glucose concentrations in the intestine cause GLUT-2 transporters to migrate to the luminal (apical) wall and, since they also transport fructose, they increase fructose absorption from the intestine.
- On the other hand, glucose may have a positive effect on the formation of GLUT-5
- Fructose intake stimulates the formation of GLUT-5, which means that completely abstaining from fructose would worsen fructose intolerance, as the body lacks the reason to form GLUT-5.
- Sorbitol should be avoided as it is suspected of inhibiting fructose absorption by inhibiting the GLUT-5 transporter. Exactly how this mechanism works has not been clarified, but experience shows that there are correlations.
- Fructose is better tolerated by many patients in the afternoon, which could be related to the circadian rhythm of GLUT-5 expression.
- High-fat food improves fructose absorption because it slows down the intestines. This means that the chyme has a longer residence time in the intestine. The few transporters can thus work longer and absorb more fructose.
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(7) Mueckler Mike, Thorens Bernard. The SLC2 (GLUT) family of membrane transporters. Molecular Aspects of Medicine 34 (2013) 121-138