Insulin Synthesis and Secretion

Insulin Synthesis and Secretion

January 16, 2020 6 By Jose Scott


This is the first video under the series Insulin and Diabetes Mellitus. Through this video, we will know how is insulin synthesized and how is it secreted from the beta cells Pancreas gland has exocrine acini and endocrine islet Insulin is secreted from the beta cells of pancreas situated at the centre of islet. Alpha cells at the periphery secrete glucagon. Delta cells secrete somatostatin and the F cells secrete pancreatic polypeptide. Now lets look at how beta cells synthesize insulin. Insulin is a peptide hormone. So, basically insulin synthesis is a protein synthesis process. The short arm of 11th chromosome on the nucleus of beta cells coats for the ins gene or the insulin gene. This gene is transcripted to form a mRNA sequence which gets translated to a signal sequence and eventually upon addition of new sequences in the rough endoplasmic reticulum pre-proinsulin is formed. This pre-proinsulin consists of the signal sequence A chain, B chain and the C chain A and B are held by three disulfide linkages. The signal sequence is cleaved off to form a proinsulin. So, the proinsulin has A, B and C chain. So, in the golgi, this proinsulin is packaged in a secretory vesicle where C peptide is cleaved off and insulin is formed and stored within the vesicle. So, what causes insulin release? When we take food, all nutrients in blood gets increased. Basically it is increased glucose that triggers the insulin release. Glucose enters inside the beta cells through GLUT-2 receptor Remember, beta cells like GLUT-2 So, the GLUT-2 receptor is present in the beta cells, the liver the intestinal cells and the kidney. GLUT-2 transport is two way transport. So, to prevent the transport out from the cells, it is phosphorylated by glucokinase to glucose-6-phosphate which undergoes oxidation to form ATP. ATP sensitive potassium channel is also present in beta cells which transfers potassium out of the cells This ATP closes the potassium channel and increases potassium ion concentration inside the cell and cause the cell to be depolarized. This depolarization causes opening of voltage gated Calcium channel which causes calcium influx. This Calcium causes release of insulin filled secretory vesicles out from the cell. This insulin secretion is biphasic. meaning it occurs in two phases. Within first few minutes of elevated blood glucose, plasma insulin increases upto 10 folds due to dumping of preformed insulin. This high insulin decreases in other five to ten minutes and again reaches a new plateau in 2-3 hours which results from additional release of preformed insulin as well as release of new insulin. What causes insulin secretion? Increased blood glucose, amino acids, fatty acids, incretins, glucagon, growth hormone cortisol parasympathetic stimulation and the beta adrenergic stimulation all increase the insulin secretion. So, what are incretins? They are the hormones secreted by the intestinal cells. Glucagon like peptide (GLP-1) and Glucose dependent insulinotropic peptide (GIP) also known as Gastric Inhibitory Peptide are two notable incretins. They increase the insulin secretion decrease glucagon secretion delay gastric emptying and promote satiety. These incretins are degraded in the body by endogeneous Dipeptidyl peptidases (DPP4) We have drugs acting on this incretin mechanism GLP agonists like Exenatide mimic the GLP action. DPP4 antagonists like Sitagliptin delay the endogenous degradation of incretins and enhance their level in blood. Factors which decrease plasma insulin level are: Decreased blood glucose, fasting alpha adrenergic stimulation and somatostatin. A lot more to learn about insulin, right? For now, just remember it as THE HORMONE OF ABUNDANCE. Thanks for watching 🙂