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#GLUT transporter

2 public questions tagged with this topic.

Which GLUT transporter has the lowest affinity for glucose?

GLUT isoforms display divergent Michaelis constants reflecting tissue metabolic roles and sensing. GLUT2 product of SLC2A2 on 3q26 expressed strongly in hepatocyte sinusoidal membrane pancreatic beta cell plasma membrane intestinal basolateral side and kidney tubule exhibits unusually high Km fifteen to twenty millimolar for glucose also transporting fructose galactose low affinity corresponding to lowest affinity among transporters. This high Km enables effective glucose sensor rather than supply line where rate varies roughly linearly across physiological plasma glucose three to fifteen millimolar without early saturation allowing liver to take up proportionally after meals for glycogen synthesis when sugar high and release glucose during fasting via glucose-6-phosphatase. In beta cells low affinity coupled with high Km glucokinase ensures metabolism proportional to blood glucose linking insulin secretion to glycemia via ATP sensitive K+ channel closure. In intestine high capacity efflux of concentrated glucose via basolateral GLUT2 prevents buildup. By contrast GLUT1 and GLUT3 low Km near one and one point five millimolar provide constitutive high affinity uptake ensuring constant brain glucose despite fluctuations and GLUT4 intermediate Km five millimolar regulated by insulin for muscle storage.

Ref: Thorens, Molecular Aspects of Medicine 2015: GLUT2 – Low Affinity Sensor Transporter.

Which GLUT transporter is insulin-dependent?

GLUT family encoded by SLC2A genes includes fourteen isoforms differing in distribution, affinity and regulation. GLUT4 product of SLC2A4 stands out as only major isoform acutely dependent on insulin via regulated exocytosis. It contains twelve transmembrane helices forming MFS fold with central glucose cavity. Basally most protein sequestered in perinuclear storage vesicles associated with TUG and VAMP2 retained by AS160 GAP keeping Rab proteins GDP-bound. Insulin activates receptor tyrosine kinase, IRS1 phosphorylation, PI3K producing PIP3, recruiting Akt2 which phosphorylates TBC1D1 and TBC1D4 relieving Rab8A, Rab10, Rab14 to GTP driving vesicle translocation, docking via exocyst and fusion via syntaxin4 SNAP23. Exercise also triggers translocation via AMPK and calcium CaMKK independent of insulin. Once inserted, GLUT4 transports glucose by facilitated diffusion Km around 5 mM matching plasma glucose, enabling rapid postprandial uptake into muscle and adipose for glycogen and triglyceride formation, crucial for glucose homeostasis and postmeal glycemic control impaired in diabetes.

Ref: Huang & Czech, Cell Metabolism 2007: GLUT4 – Insulin-Dependent Glucose Transporter.