1. Glucose Transport Across Cell Membranes
Glucose is a polar molecule and cannot freely cross the hydrophobic lipid bilayer of cell
membranes. Cells rely on specialized glucose transport proteins to facilitate its movement.
There are two main types of glucose transport mechanisms:
- Passive transport, where glucose moves down its concentration gradient through
facilitative transporters without energy input.
- Active transport, where glucose moves against its concentration gradient, requiring
energy, often from ATP or ion gradients.
In humans, several glucose transporter (GLUT) isoforms exist, each adapted to specific
tissues and physiological conditions. These are isozymes — structurally distinct proteins
performing the same function of glucose transport.
GLUT1 and GLUT3 are widely expressed and have a high affinity for glucose (Km ~1 mM),
ensuring efficient glucose uptake even when blood glucose levels are low. They are
especially abundant in red blood cells, brain, heart, and other tissues with high glucose
demand.
GLUT2 has a much lower affinity (Km ~15–20 mM), functioning primarily in the liver and
pancreatic beta cells as a glucose sensor. It allows the liver to take up glucose efficiently
when blood glucose levels are elevated, such as after meals, and stimulates insulin secretion
from the pancreas.
GLUT4 is insulin-sensitive and primarily found in muscle and adipose tissue. It is stored
intracellularly and translocated to the plasma membrane in response to insulin, enhancing
glucose uptake for energy storage and utilization.
GLUT5 primarily transports fructose and is found in the small intestine and sperm cells.
Understanding the kinetics (Km) of these transporters helps explain their physiological
roles. A low Km means high affinity, so transporters saturate at low glucose concentrations.
High Km transporters are activated only when glucose is abundant.
2. Hormonal Regulation of Glucose Metabolism
Insulin is a peptide hormone secreted by the beta cells of the pancreatic islets in response to
rising blood glucose levels. It promotes glucose uptake and utilization by multiple
mechanisms:
- Insulin stimulates the translocation of GLUT4 transporters to the muscle and adipose cell
membranes, increasing glucose entry.
- It activates glycolytic enzymes and inhibits gluconeogenic enzymes, shifting metabolism