Glucose Signalling Pathwat

A meal causes an increase in glucose

Glucose enters pancreatic B cells through glucose transporters

In pancreatic B cells

Glucose is metabolized, producing additional ATP

B cells have

ATP sensitive potassium channels. When ATP levels rise, potassium channels close

Closing potassium channels

depolarizes the cell, because less K+ is leaving the cell.

Depolarization of the cell

opens voltage-gated calcium channels in the plasma membrane.

Calcium diffuses into the cell

Rise in the intracellular calcium concentration causes insulin containing secretory vesicles to fuse with the B cell membrane

Insulin is released from B cells in the pancrease

Insulin binds to a subunits on the extracellular side of the insulin receptor

Receptor dimerizes

B subunits kinase domain uses ATP to autophosphorylates tyrosine residues on the adjacenet receptor tail. This happens because ATP’s terminal phosphate is transfered on to the hydroxyl group of a tyrosine R group on the receptor tail

Phosphorylates tyrosine receptors

act as docking sites for additional adaptor proteins. IRS binds to the active insulin receptor tail.

When IRS binds

The receptor’s activated tyrosine-kinase domain uses ATP to phosphorylate multiple tyrosine residues on IRS-1.

Phosphorylated IRS

can recruit several signaling protiens and amplify the insulin signal

Activated IRS

is recognized by the regulatory portion of P13K, which binds to IRS-1. This brings P13K close to the inner plasma membrane and its lipid substrate PIP2.

When P13K is recruited to IRS-1

it uses ATP to add a phosphate to PIP2 converting it to PIP3

PIP3 acts as a docking lipid

recruits Akt and kinases that activate AKT

Akt is phosphorylated and becomes active

Akt signals for GLUT4-containing vesicles to move to and fuse with the plasma membrane. This increases the number of GLUT4 transporters available at the cell surface.

GLUT4 provides a hydrophilic pathway through the nonpolar membrane for glucose.

Glucose moves through GLUT4 by facilitated diffusion