Insulin Synthesis

Insulin Synthesis

The discovery of insulin was one of the greatest events in medical history. The existence of insulin is as necessary as that of glucose (the body’s basic unit of fuel). Both of them are related and required for life. In order for the glucose to be regulated, insulin circulates through blood vessels and bind with particular (insulin) receptors, promoting interactions essential for the wellbeing of the body’s internal mechanisms.

Insulin is a hormone synthesized exclusively by the pancreatic beta cells. These beta cells are located in the pancreas in clusters known as the islets of Langerhans. Insulin is a small protein produced as part of a larger protein to ensure it folds properly. In the protein assembly of insulin, the messenger RNA transcript is translated into an inactive protein called preproinsulin. Preproinsulin contains an amino-terminal signal sequence that is required in order for the precursor hormone to pass through the membrane of the endoplasmic reticulum (ER) for post-translational processing. The post-translational processing clips away those portions not needed for the bioactive hormone. Upon entering the ER, the preproinsulin signal sequence, now useless, is proteolytically removed to form proinsulin. Once the post-translational formation of three vital disulfide bonds occurs, specific peptidases cleave proinsulin. The final product of the biosynthesis is a mature and active insulin. Finally, insulin is packaged and stored in secretory granules, which accumulate in the cytoplasm, until release is triggered.

Insulin is released from beta cells as a response to the alterations in blood glucose concentration. The type 2 glucose transporters (GLUT2) mediate the entry of glucose into beta cells; this glucose is phosphorylated by the rate-limiting enzyme glucokinase and becomes effectively trapped within the beta cells and is further metabolized to create ATP (the energy molecule). The increased ATP and ADP ratio causes the ATP-gated potassium channels in the cellular membrane to close up, preventing potassium ions from being pushed across the cell membrane. Due to the increased concentration of potassium ions, a rise of positive charges inside the cell leads it to its depolarization. Having as a direct effect, the activation of voltage-gated calcium channels, whose role is to transport calcium ions into the cell. The brisk increase in intracellular calcium concentrations triggers export of the insulin-storing granules by a process known as exocytosis. The ultimate result is the export of insulin from beta cells and its diffusion into nearby blood vessels. Extensive vascular capacity of surrounding pancreatic islets ensures the prompt diffusion of insulin (and glucose) between beta cells and blood vessels. Insulin release is a biphasic process. The initial amount of insulin released upon glucose absorption is dependent on the amounts available in storage. Once depleted, a second phase of insulin release is initiated. This latter release is prolonged