SN7 SHORT NOTE 5M

Describe the glucose transporters with their sites and functions.

Biochemistry · 1st Professional — Pre-Clinical

Definition

Glucose transporters (GLUT) = a family of membrane proteins that carry glucose across cell membranes by facilitated diffusion — down its concentration gradient, without ATP.

Distinct from the SGLT family, which perform secondary active transport coupled to sodium

The Glut Family

Transporter	Site	Km	Special feature
GLUT-1	Brain, RBC, placenta, blood–brain barrier	Low (1 mM)	Basal uptake; ensures a constant supply to the brain
GLUT-2	Liver, pancreatic β cell, kidney, intestine	High (15–20 mM)	Bidirectional; acts as the glucose sensor of the β cell with glucokinase
GLUT-3	Neurones, placenta	Very low (1 mM)	Highest affinity — neurones get priority
GLUT-4	Skeletal muscle, cardiac muscle, adipose tissue	Low (5 mM)	The insulin-dependent one
GLUT-5	Intestine, testis	—	Fructose transporter, not glucose

Glut-4 and Insulin Action

Insulin binds its receptor → Tyrosine kinase → IRS-1 → PI3-kinase → GLUT-4 vesicles translocate to the cell membrane → ↑ Number of transporters on the surface → ↑ Glucose uptake into muscle and fat

Insulin increases uptake 10–40 fold in these tissues
Exercise also recruits GLUT-4, independently of insulin, through AMPK — the biochemical reason exercise lowers blood glucose in diabetes

CLINICAL PEARL

Brain, liver, RBC and kidney take up glucose without insulin. This is why the brain is spared in diabetes but is the first organ to suffer in hypoglycaemia, and why insulin deficiency causes hyperglycaemia while the brain still functions.

SGLT — Active Transport

Transporter	Site	Function
SGLT-1	Intestinal mucosa, renal PCT (S3)	Absorbs glucose against its gradient, coupled to Na+. The basis of oral rehydration solution
SGLT-2	Renal PCT (S1, S2)	Reabsorbs 90% of filtered glucose

Applied Aspects

SGLT-2 inhibitors (dapagliflozin, empagliflozin) deliberately block renal glucose reabsorption → glycosuria → lower blood glucose independently of insulin; they also reduce cardiovascular and renal events
ORS works because SGLT-1 remains intact in cholera — glucose must be present for sodium and therefore water to be absorbed. A purely saline solution would not work
GLUT-1 deficiency syndrome — impaired glucose transport across the blood–brain barrier → infantile seizures and developmental delay; treated with a ketogenic diet, since ketones use a different transporter
GLUT-4 dysfunction is central to the insulin resistance of type 2 diabetes and obesity
Fanconi–Bickel syndrome — GLUT-2 defect → hepatomegaly with a renal tubular defect
Fructose malabsorption follows a GLUT-5 defect → osmotic diarrhoea and bloating after fruit or sweetened drinks

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