Glucose Transporters GLUT and SGLT: Biochemistry, MCAT, and USMLE

Glucose traffic is operated by two families of glucose transports: the GLUT family and SGLT family. The GLUT family consists of 14 different types of glucose transporters from GLUT-1, GLUT-2, GLUT-3 all the way up to GLUT-14. The SGLT family consists of sodium-glucose cotransporters, including SGLT1 and SGLT2.

Glucose transporters; Source: Wiki Commons

GLUT vs SGLT: Differences between GLUT and SGLT

Glucose transporters in the GLUT family use facilitative diffusion to transport glucose across the plasma membrane. They are enzyme proteins that can also transport galactose and fructose, in addition to glucose. GLUTs are expressed in a wide variety of cells, from red blood cells to liver to the brain.

Please see the section below “Different Types of GLUT” to learn more about which GLUT types for which tissue types.

Sodium-glucose cotransporters in the SGLT family, based on their name, use active transport to transport both sodium and glucose into cells. SGLTs are enzyme proteins that take up glucose into cells against an electrochemical gradient, and take up sodium ions down their concentration gradient. SGLTs are expressed in the small intestine and renal proximal tubules.

Which type of glucose transporter would transport glucose across the cell membrane against the concentration gradient?
GLUT Glucose Transporter SGLT Sodium-Glucose Cotransporter
Uses facilitative diffusion Uses active transport (needs energy)
Transports glucose Co-Transports both glucose and sodium
Uniport Symport
Can also transport galactose and fructose n/a
Glucose uptake down concentration gradient Glucose uptake against concentration gradient; Sodium uptake down concentration gradient
Location in all tissues (see below for which types for which tissues) Location only in small intestine and renal proximal tubules
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Where are SGLT transporters not expressed?
Red blood cells
Small intestine
Renal proximal tubules

Biochemistry Structure of Glucose Transporters (GLUTS)

Structure of GLUT (Source: Research Gate)

The structure of a generic GLUT glucose transporter is made up of 4 subunits per transporter. For 1 subunit, there are 12 transmembrane domains. There are 1 large extracellular loop 1 and 1 large intracellular loop 3. Amino and carboxy terminal groups are in the cytoplasm.

How many total transmembrane domains are there for a standard GLUT glucose transporter?

Different Types of Glucose Transporters GLUT and their Major Tissue Expression

GLUT 4 with insulin; Insulin induces GLUT4 vesicles to transport GLUT 4 into the plasma membrane. GLUT 4 then takes up glucose (Source: Wiki Commons)

There are 14 different types of glucose transporters with different tissue specificities and affinities for glucose. We will explain 5 of the most important GLUT transporters.

Glut-1: Major Tissue Expression in Erythrocytes and the Brain: High Affinity for Glucose: Low Km (1mM): Insulin Independent

Glut-2: Major Tissue Expression in Liver and Pancreas: Lower affinity for Glucose: High Km (15-20 mM): Insulin Independent

Glut-3: Major Tissue Expression in Brain (neuronal): High Affinity for Glucose: Low Km (1mM): Insulin Independent

Glut-4: Major Tissue Expression in Muscle, Adipose, and Heart: Medium affinity for Glucose: Medium Km (5 mM): Insulin Dependent

Glut-5: Major Tissue Expression in Intestine, Testis, and Kidney: Prefers fructose over glucose

Mnemonic Memory Aid: Fructose has 5 carbons, so GLUT 5 transports fructose.

Which GLUT glucose transporter is expressed in the brain?
Protein Major Tissue Expression Km Affinity for Glucose Insulin-Independence?
GLUT 1 Brain, erythryocytes 1 mM High Yes  
GLUT 2 Liver, Pancreas 15-20 mM Low Yes  
GLUT 3 Brain 1 mM High Yes  
GLUT 4 Muscle, adipose, heart 5 mM Medium No  
GLUT 5 Intestine, testis, kidney Prefers fructose n/a Yes  
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Which of the following GLUT glucose transporters have a low affinity for glucose?

How does the Small Intestine take up and transport glucose?

The small intestine epithelia absorb glucose, galactose, and fructose, and has at least 3 hexose transporters to transport glucose, galactose, and fructose, across the cell membrane.

The small intestine cell has 2 sides: apical membrane and the basolateral membrane. The apical membrane faces the intestinal lumen, where there are lots of sugars and sodium from our food. The basolateral membrane faces the extracellular fluid, or our blood. The goal of the small intestine epithelium is to transport glucose from the intestinal lumen into the blood.

The apical membrane has 2 transporters: SGLUT1 and GLUT 5. Anything with S in front of GLUT can also transport sodium with glucose. Likewise, SGLUT1 is a cotransporter that takes up glucose/galactose with sodium from the lumen. GLUT 5 transports fructose, taking up fructose from the intestinal lumen into the small intestine cell.

The basolateral membrane has 2 main transporters as well: GLUT 2 and Na/K ATPase. GLUT 2 transports fructose out into the blood. Na/K ATPase takes the sodium (that was transported in earlier from SGLUT 1) and dumps it out into the blood as well, while taking up K potassium into the cell.

Which of the following GLUT glucose transporters is NOT insulin-independent? And which tissue is this glucose transporter mainly expressed in?
GLUT4; Muscle and Heart
GLUT4; Intestine
GLUT1; Brain and RBC’s
GLUT2; Liver and Pancreas
GLUT2; Muscle and Heart
GLUT3; Brain
GLUT5; Intestine and Kidney
GLUT3; Liver and Pancreas

Works Cited:

Brown, G.K. Glucose transporters: Structure, function, and consequences of deficiency. Journal of Inherited Metabolic Disease. May 2000, Volume 23, Issue 3, 237-246.

Thorens, B., & Mueckler, M. Glucose transporters in the 21st Century. American Journal of Physiology. Feburary 2010.

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