Tubular reabsorption of glucose

Definitions & Key takeaways

Tubular reabsorption of glucose is an important process that occurs in the kidneys to maintain normal blood glucose levels. When blood is filtered through the glomeruli in the kidneys, glucose is freely filtered into the tubular fluid of the nephron. In a healthy individual, nearly all of this filtered glucose is reabsorbed back into the bloodstream through the proximal tubule of the nephron. The reabsorption of glucose is facilitated by glucose transporters, primarily SGLT2 and SGLT1, which move glucose from the tubular fluid into the cells and then into the bloodstream.

Chapters:

Watch video only

Introduction0:00–1:32

Glucose is found in almost every food we eat, like bread, potatoes, or fruit. Once it’s absorbed by the body, it’s converted into a source of energy.
The body needs the plasma glucose levels to remain within a pretty narrow range, between 70 mg/dl to 110 mg/dl, when you’ve had nothing to eat and less than 140 mg/dl after a meal.
Now, the entire blood volume is about 5 liters, and the plasma volume is about 3 liters of that. The kidneys filter the entire plasma volume 60 times a day, which means that means our kidneys filter approximately 180 liters of plasma each day!
If each liter of plasma contains about 1 g of glucose, this means about 180 g of glucose get filtered by the kidneys per single day.
That’s the filtration rate of glucose. If you had a blood glucose concentration of 1.5 g of glucose per L, you’d end up with a filtration rate of glucose of 270 g / day.
Essentially, the higher the plasma glucose concentration, the more glucose will get filtered. If we wanted to illustrate that in a graph, with plasma glucose concentration on the x axis and glucose filtration rate on the y axis, we would see that as the plasma glucose concentration increases, the filtered load of glucose increases linearly.

Kidney1:32–2:05

Now, looking at the kidney, specifically inside the kidney, there are two main parts, the outer cortex and the inner medulla.
If we zoom in, there are millions of tiny functional units called nephrons which go from the outer cortex down into the medulla and back out into the cortex again.
Each nephron is made up of the glomerulus, or a tiny clump of capillaries, where blood filtration begins. When glucose enters the glomerulus, some of it gets filtered into the renal tubule.

Renal Tubules2:05–2:31

Zooming in on one of these renal tubules, each one is lined by brush border cells which have two surfaces. One is the apical surface which faces the tubular lumen and is lined with microvilli, which are tiny little projections that increase the cell’s surface area to help with solute reabsorption.
The other is the basolateral surface, which faces the peritubular capillaries, which run alongside the nephron. Now, the body needs glucose and doesn’t want glucose getting lost in the urine, so it tries to reclaim this filtered glucose right away, in the first segment of the renal tubule, known as the proximal convoluted tubule.

Glucose Clearance2:31–2:58

Now, more than 99% of the filtered load of glucose is reabsorbed back into the circulation. But, that doesn’t just happen, there are, obviously, a couple steps to take to accomplish this.

Facilitated Diffusion2:58–4:05

First, the glucose needs to crosses the apical surface of the renal tubule cells. But normally, the glucose concentration inside the cells is much higher than that inside the tubule, so for glucose to cross the apical surface requires energy.
Fortunately, the electrochemical gradient of sodium drives it to move inside the cell, and that sodium gradient is sufficient to pull glucose into the tubule cell as well.
More specifically, there’s a sodium- glucose linked transporter, or SGLT that moves glucose against its concentration gradient - a process called secondary active transport.
SGLT binds two sodium ions and one glucose molecule from the tubular fluid and releases them inside the cell. The intracellular concentration of glucose is high so it quickly moves across the basolateral membrane through the process of diffusion, and makes its way into peritubular capillaries specialized glucose transporters, called GLUT1 or GLUT2.
This process is known as facilitated diffusion. We can summarize this process of glucose reabsorption using the same graph as before, but with plasma glucose concentration on the x axis and glucose reabsorption rate on the y axis.

Glucose Reabsorption4:05–5:52

Initially, all of the filtered glucose gets reabsorbed back into the bloodstream, so the curve would match the filtration rate line.
But, there’s only a limited number of glucose transporter proteins available, which means that if they are all busy moving glucose, additional glucose molecules won’t speed things up anymore.
That starts happening at a glucose plasma concentration of approximately 200 mg/dl, and once the glucose concentration is even higher - around 350 mg/dl, all of the carriers are fully saturated.
That difference between 200 mg/dl and 350 mg/dl is because of the variation in the functioning of individual nephrons. But beyond 350 mg/dl all of the carrier protein in virtually all of the nephrons are occupied by glucose molecules, so there are no more available to reabsorb the rest of the filtered glucose.
So that makes the reabsorption curve level out at its maximal point, which is known as ™ or transport maximum,. It also means that the excess glucose, which is the filtered glucose minus the reabsorbed glucose, gets excreted in the urine.
The point at which this starts happening is called threshold. We can draw out a final curve called the excretion rate of glucose on the y axis.
It’s literally, just the difference between the two curves, and the initial curved part of the line as it’s going from no excretion to linear excretion is sometimes referred to as the splay.

Glycosuria5:52–6:43

Now, glycosuria or glucose in the urine is never normal, and it often occurs in uncontrolled diabetes mellitus, where the lack of insulin results in whooping levels of plasma glucose, well above the threshold of 200 mg/dl.
But keep in mind that a more mild abnormality in glucose concentration like 150 mg/dl may not cause glucosuria, because the threshold hasn’t been reached yet.
On the flip side, sometimes the plasma glucose concentration is totally normal, but glycosuria still occurs. For example, hormonal changes during pregnancy lead to increased blood flow to the kidneys.
The increased blood flow means that more glucose gets filtered than usual and that may be enough to exceed the reabsorption threshold.
All right, as a quick recap, normally below a blood glucose concentration of 200 mg/dl, all of the filtered glucose is reabsorbed back into the bloodstream, and by the same token, none of the glucose is excreted.

Review6:43–7:28

Between 200 mg/dl and 350 mg/dl, glucose transport proteins start hitting their saturation point, so some of the filtered glucose appears in the urine for the first time, known as threshold, and this gradual increase is referred to as the splay.
Above 350 mg/dL, all of the carrier proteins are fully saturated, known as the transport maxium, so the excretion rate of glucose rises linearly with the filtration rate.