New

Glucose Transporters

Neelam Maurya

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 glucos

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 Question

GLUCOSE TRANSPORTERS

Transport of glucose –

  • Into cells – By “Facilitated diffusion”.
  • In intestine & kidney – By “Secondary active transport” with Na2+.
1. SODIUM-DEPENDENT GLUCOSE TRANSPORTERS (SGLT):
  • Present in small intestine & kidneys
  • Acts via secondary active transport.
  • Coupled with the Na2+-K+-ATPase pump. 
  • Hence, referred “Na2+- Glucose Co-transport” mechanism.
TRANSPORTER LOCATION
 SGLT – 1 Small intestine & renal tubules
 SGLT – 2 Renal tubules 

2. SODIUM-INDEPENDENT GLUCOSE TRANSPORTERS (GLUT):

  • Acts via facilitated diffusion of glucose across the cell membrane.
TRANSPORTER LOCATION FUNCTION
GLUT – 1
  • Placenta.
  • Brain.
  • RBC.
  • Basal glucose uptake.
GLUT – 2
  • B cells of islets.

 
  • B-cell glucose sensor.
GLUT – 3
  • Neurons.
  • Basal glucose uptake.
  • High affinity for glucose.
GLUT – 4
  • In Heart (cardiac muscle).
  • Skeletal Muscle
  • Adipose Tiissue
  • lnsulin-dependent Glucose Uptake.
  • Reduced in fasting state, when the insulin levels are low.
GLUT – 5
  • Jejunum.
  • Sperm.
  • Fructose transport.
  • Hence “Fructose transporter”.
GLUT – 8
  • Blastocyst.
  • Insulin-responsive glucose transporter of Blastocyst.

Inhibitors of glucose transporters:

  • Phlorizin & Phloretin.
  • Phlorizin – Phloretin 2β Glucoside.
Don’t Forget to Solve all the previous Year Question asked on Glucose Transporters