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Insulin Secretion

Notes

Insulin Secretion

Now, let's transition to insulin secretion.

  • Draw a pancreatic beta cell as a circular outline.
  • Within it show some secretory granules.
    • It is these granules that, upon stimulation, will exocytose and release insulin.

Let's see how.

  • On the surface of the beta cell, draw:
    • A voltage-dependent calcium channel that is closed.
    • An ATP-sensitive potassium channel.
    • GLUT2: a glucose transporter.
  • Indicate that K+ flows down its concentration gradient out of the cell through the potassium channel. - This gradient is maintained by a sodium potassium pump, which we do not include here.

Now, imagine that you eat a carbohydrate rich meal. Your plasma glucose levels are high!

  • Show that glucose enters a pancreatic beta cell via GLUT2.
    • From here, glycolysis occurs, in which the cell breaks down glucose to synthesize ATP.
  • Draw the first step of glycolysis: the enzyme glucokinase phosphorylates glucose to glucose 6-phosphate and traps it in the cell.
  • Show that glucose-6-phosphate breaks down to ATP (we will not draw the carbohydrate intermediates).
  • Show that ATP binds the potassium channel.
    • Indicate that this binding causes it to close.
    • This depolarizes the membrane, which activates the voltage-dependent calcium channel.
  • Show that the calcium influx promotes exocytosis and the release of insulin we mentioned at the beginning of this section.
  • Thus, high plasma glucose stimulates the beta cell to secrete insulin, and it relies on GLUT2 and glucokinase to sense increases in plasma glucose levels.
  • Indicate that GLUT2 transporters are tissue-specific: they are only present in pancreatic beta cells and liver cells.
  • More importantly, write that they have a high Km; thus, they only bind glucose when plasma glucose is high.
  • As for glucokinase, indicate that it is also specific to the liver and pancreas.
  • And indicate that:
    • It has a high Km (like GLUT2) and it also has a high Vmax.
    • It is not inhibited by its product, glucose-6-phosphate. It can continue trapping glucose in the cell even when intracellular concentrations rise.
  • Thus, write that pancreatic beta cells are the most important glucose-sensing cells in the body, and they rely on GLUT2 and glucokinase!