GLUCOSE TRANSPORTERS

GLUCOSE TRANSPORTERS

Transport of glucose –

Into cells – By “Facilitated diffusion”.

In intestine & kidney – By “Secondary active transport” with Na²⁺.

Mediated mainly by 2 sets of transporters –

Sodium-dependent Glucose Transporters (SGLT).

Sodium-Independent Glucose Transporters (GLUT).

1. SODIUM-DEPENDENT GLUCOSE TRANSPORTERS (SGLT):

Have 12 transmembrane domains.

Present in small intestine & kidneys

Acts via secondary active transport.

Unidirectional.

Coupled with the Na²⁺-K⁺-ATPase pump.

– Hence, referred “Na²⁺– Glucose Co-transport” mechanism.

Types:

SGLT-1 & SGLT-2.

TRANSPORTER	LOCATION	FUNCTION
SGLT – 1	Small intestine & renal tubules	Absorption of glucose
SGLT – 2	Renal tubules	Absorption of glucose

CLINICAL CORRELATION:

Renal Glycosuria

– Isolated glucosuria in presence of normal blood glucose concentration.

– Due to mutations in SLC 5A2.

– SLC 5A2 – Gene encoding high-capacity sodium-glucose co-transporter SGLT-2 in proximal renal tubule.

2. SODIUM-INDEPENDENT GLUCOSE TRANSPORTERS (GLUT):

GLUT – Family of closely related proteins spanning the cell membrane 12 times.

– Acts via facilitated diffusion of glucose across the cell membrane.

– Passive process down the concentration gradient.

Bi-directional.

– Ping-pong mechanism.

– Is Sodium independent mechanism.

Types:

Includes a number of transporters ranging from GLUT – (1 – 12).

TRANSPORTER	LOCATION	FUNCTION
GLUT – 1	Placenta. Blood-brain barrier. Retina. Brain. RBC. Kidney. Colon	Basal glucose uptake.
GLUT – 2	B cells of islets. Liver – Sinusoid membrane. Epithelial cells of small intestine & kidney. Especially, On serosal-side (Basolateral side) of Intestinal Cell. On Basolateral membrane of PCT in Kidney.	B–cell glucose sensor. Transport out of intestinal & renal epithelial cells. In liver – Excess glucose removal from blood. In pancreas – Insulin release regulation. Low affinity & higher Km.
GLUT – 3	Neurons, Placenta & Kidney	Basal glucose uptake. High affinity for glucose.
GLUT – 4	In Heart (cardiac muscle). Skeletal Muscle. Adipose Tiissue	lnsulin-dependent Glucose Uptake. – I.e., “Insulin stimulating” process. Reduced in fasting state, when the insulin levels are low.
GLUT – 5	Jejunum. Sperm.	Fructose transport. Hence “Fructose transporter”.
GLUT – 6	Spleen & in Leukocytes. Mostly “Pseudogene”.	Possibly no transporter function.
GLUT – 7	Liver Endoplasmic reticulum	G-6-P transporter in Endoplasmic Reticulum.
GLUT – 8	Testis. Blastocyst. Brain	Insulin-responsive glucose transporter of Blastocyst. Glucose transporter to mature spermatozoa.
GLUT – 9	Liver. Kidney.	Urate transporter.
GLUT – 10	Liver. Pancreas.	Nil
GLUT – 11	Heart. Skeletal muscle	Also a “Fructose transporter”.
GLUT – 12	Prostate. Heart. Mammary gland. White adipose tissue.	Insulin-responsive.

FACTORS INFLUENCING:

Inhibitors of glucose transporters:

Phlorizin & Phloretin.

1. Phlorizin –

Phloretin 2β Glucoside.

Inhibitor of sodium-dependent glucose transporter.

By competing with D Glucose-binding carrier sites.

Affinity – SGLT-2 > SGLT-1.

2. Phloretin –

Aglycone of Phlorizin.

Inhibitor of facilitated diffusion by GLUT-1 or GLUT-4.

IMPORTANT POINTS TO REMEMBER:

TRANSPORTER INVOLVED	FACT TO REMEMBER
GLUT – 1	Widely distributed glucose transporter. Most abundant Glucose transporter in RBC. Major glucose transporter of Brain & Placenta. – Yet, absent in neurons.
GLUT – 3	Present in neurons.
GLUT – 4, 8 & 12	Insulin-dependent Glucose transporters.
GLUT – 8	Glucose transporter of blastocyst. Insulin-dependent glucose transporter.
GLUT – 9	Urate transporter.

VARIATIONS IN ABSORPTION WITH TYPES:

Glucose & galactose absorbed by sodium-dependent process.

– Carried by same transport protein (SGLT 1).

– Compets each other for intestinal absorption.

Fructose absorbed down their concentration gradient by GLUT 5.

All the sugars exit from intestinal cells via GLUT 2.

Exam Important