GLUT-2 Transporter Function

• GLUT-2 has a weak affinity for glucose, with a Km of 15 mM
• GLUT-2 is found in beta cells of the pancreas, liver, gastrointestinal tract (GIT), and nephrons.

GLUT-2 in Enterocytes

• Mucosal cells are a general term, while enterocytes are a specific type of mucosal cell.
• GLUT-2, along with GLUT-1, is used in enterocyte cells of the small intestine on the basolateral side to help glucose move to the blood.
• When glucose concentration is high in the lumen (around 30mM), GLUT-2 channels are also present on the apical membrane to facilitate glucose diffusion from the small intestine into the cell.

GLUT-2 in Pancreas Beta Cells

• Beta cells are clustered in the pancreas, surrounded by alpha cells, with delta cells scattered around.
• Beta cells release insulin when blood glucose levels rise.
• Glucose diffuses into beta cells through GLUT-2 channels.
• Glucokinase phosphorylates glucose, preventing it from leaving the cell; GLUT-2 and glucokinase together form a glucose sensor.
• Glucokinase converts glucose into glucose-6-phosphate, which is irreversible.
• Glucose-6-phosphate is converted into pyruvate through glycolysis, and pyruvate enters the Krebs cycle in the mitochondria to produce ATP.
• ATP plugs K+ pumps, causing K+ buildup and cell depolarization.
• Depolarization opens voltage-sensitive Ca2+ channels, bringing Ca2+ into the cell.
• Ca2+ modifies surface proteins of insulin storage granules (ISG) and their receptors on the cell membrane, bringing them together.
• Snare proteins on the ISG surface facilitate the movement of the ISG towards the cell membrane.
• The ISG fuses to the membrane and releases insulin into the blood.

GLUT-2 in the Liver

• Insulin sensors on the hepatocyte surface capture insulin.
• Stimulation of these receptors activates genes that stimulate glucokinase activity.
• When glucose levels are low, glucokinase regulatory protein (GKRP) grabs glucokinase and moves it to the nucleus.
• When glucose levels rise, some glucose goes to the nucleus and causes glucokinase to leave the nucleus and phosphorylate glucose.
• Glucose entering the hepatocyte is immediately phosphorylated and converted into glucose-6-phosphate by glucokinase.
• Glucose-6-phosphate can proceed through three different pathways: conversion into glycogen until glycogen stores are full (about 10% of liver weight), conversion into hexose-monophosphate-shunt, or glycolysis to become pyruvate.
• Pyruvate undergoes the Krebs cycle, resulting in citrate.
• G6P → Glyceraldehyde 3 Phosphate → Pyruvate → Adenyl coA → Citrate
• Citrate goes to the cytosol and is converted back to acetyl-CoA, which binds to create long carbon chains that become fatty acids.
• Three fatty acids bind with glycerol (from glyceraldehyde) to create triglycerides.
• Triglycerides are packed into special proteins and thrown into the blood as VLDL (Very Low-Density Lipoprotein).
• Lipoprotein lipases on the endothelium of blood vessels strip fatty acids from triglycerides as VLDL passes by.
• Glycerol and fatty acids are separately absorbed into adipocytes (fat cells).

Glucokinase Location

• Glucokinase is found in hepatocytes (glucose storage), pancreatic beta cells (assists in the release of insulin), and the hypothalamus (glucose sensors, especially in hypoglycemic situations).