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III.3.B.c. The Glu-sensing of B cells in pancreatic islets of Langerhans

The membrane of the B cells contains facilitative GLUT-2 transporters, which ensure the uptake of Glu into the cells.

In the cells, the enzyme glucokinase phosphorylates Glu, this reaction converting Glu to pyruvate, and ATP is generated from pyruvate in the mitochondria. ATP-sensitive potassium (K+) channels are closed by ATP, so that the positively charged K+ ions cannot leave the cell, and the cell is depolarized. The depolarization results in the opening of voltage-gated Ca2+ channels, and Ca2+ enters the cell, which enhances depolarization. The higher level of depolarization leads to the exocytosis of insulin stored in crystalline form with Zn2+ in granules (Fig. 4).  

The synthesis of insulin is probably stimulated by glucose-6-phosphate.

The function of B cells is tested by the Arg tolerance test.

The intake of Arg into B cells does not occur through GLUT-2 transporters. In the cell, ATP is generated from Arg, which induces the exocytosis of insulin. If the Arg tolerance test indicates insulin release, but the OGTT does not, the GLUT-2 transporters are damaged. In this case, sulfonylurea derivatives are used. The sulfonylurea derivatives bind to the K+ channels from outside the cell, and the channels are therefore closed reversibly. The above-described depolarizing reactions lead to the exocytosis of insulin. Patients with this problem have to take a pill containing sulfonylurea derivatives before eating.     

Figure 4. The Glu sensing of pancreatic B cells

(red arrow = inhibition, green arrow = stimulation)