Question

Explain the pathway used in the formation of insulin in pancreatic beta islet cells. Start from the DNA and end with secretion from the cell.

Answer 1

Increase in glucose levels detected by the pancreatic beta cells ,which causes synthesis and release of insulin ,

Synthesis of insulin begins within the nucleus by the transcription of insulin gene ,DNA polymerase make the copy of insulin gene as mRNA,after the splicing of mRNA ,it is ready to be translated ,the mRNA leaves the nucleus and attaches to the ribosome ,the ribosome translates the mRNA in to the protein which is of about 110 aminoacids in length,this protein is called preproinsulin, it had a signal peptide of 24 amino acids in length which helps to cross cell membrane ,for further processing the preproinsulin enters endoplasmic reticulum where it converts to proinsulin by proteases ,it had three parts: amino terminal b chain ,carboxy terminal a chain ,connecting c-peptide .C-peptide is removed from the proinsulin by various peptidases which forms free insulin and c-peptide ,these are packaged in to secretory granules in Endoplasmic reticulum.

Preproinsulin-----proinsulin----Insulin+ C-peptide

Glucose levels in the blood are monitored by the beta cells ,glucose enters the beta cells from blood through GLUT-2 transport ,where it is metabolized to produce ATP ,this ATP binds to ATP sensitive K+ channels and close them as the potassium cannot leave it leads to depolarization ,it causes calcium to enter the beta cells,this calcium uptake by the beta cell causes exocytosis ,presynthesized secretory vesicles containing insulin which then released in to the blood ,it leaves pancreas and travels throughout the body ,it will bind to the insulin receptors located on the muscle and fat cells ,it activates secondary messenger system which causes translocation of glucose transporter GLUT-4 in to the cell membrane ,this GLUT-4 causes the glucose to leave the blood and to enter muscle and fat cells and can be converted in to the fat or stored as glycogen or can be utilized to make ATP.