Question

Using the knowledge you’ve gathered about gene expression, cells, and membrane transport, describe the journey of the protein-hormone insulin from its gene to its export from the cells in your pancreas. Describe the processes and organelles involved in this process.

Answer 1

Insulin is a small protein and is composed of two chains held together by disulphide bonds. Humans have a single insulin gene, INS, located on chromosome II.

Insulin is produced by pancreatic beta cells. Insulin is translated initially as preproinsulin., which is then processed to proinsulin i n the RER(Rough endoplasmic reticulum) upon cleavage of its signal sequence by a signal peptidase. In the RER, proinsulin is folded and stabilised in its 3D proinsulin configuration, linking the semihelical A domain and helical B domain via the formation of disulphide bonds. After transit to the golgi apparatus, the properly folded proinsulin is sorted into still-immature secretory granules where it is processed via the prohormone covertases PC1/3 and PC2, which cleave the C-peptide. Susequently, carboxypeptidase E removes C-terminal basic amino acids from the resulting peptide chains, yielding mature insulin consisting of A- and B-peptide chains linked by disulfide bonds.

Insulin and C-peptide are packaged in the Golgi bodies into secretory granules which accomodate in the cytoplasm.

When the beta cell is appropriately stimulated, insulin is secreted from thr cell by exocytosis and diffuses into islets capillary blood.

Insulin is secreted primarily in response to elevated blood concentrations of glucose. But some neural stimuli and increased blood concentrations of other fuel molecules including amino acids and fatty acids also promote insulin secretion.

Glucose is transported into the beta cell by facilitated diffusion through a glucose transporter, elevated concentrations of glucose in extracellular fluid lead to elevated concentrations of glucose within the beta cell.

Elevated concentrations of glucose within the beta cell ultimately leads to membrane depolarization and influx of extracellular calcium. The resulting increse in intracellular calcium is the primary trigger for exocytosis of insulin-containig secretory granules.