Question

It is known that glucose entering the blood from the digestive tract causes a more significant increase in the insulin content in the blood compared to the same amount of glucose, but administered intravenously. Explain this phenomenon, taking into account the results of the synthesis and secretion of insulin by beta-cells of the pancreatic islets of Langerhans.
For the answer:
1. Write the name of the molecules involved in regulating the secretion of insulin betta by the cells of the pancreas
2. describe the steps in the synthesis and secretion of insulin and the role of glucose in this process;
3. indicate which transmembrane mechanisms are used by the Gastric inhibitory polypeptide, the Glucagon-like peptide, which are secreted by the cells of the small intestine mucous membrane when carbohydrates and Cholecystokinin enter them to transmit signals to beta cells
4. why the effect of the Gastric inhibitory polypeptide and the glucagon-like peptide on beta cells appears earlier than the effect of the main activator of insulin secretion - glucose.

Answer 1

The incretin effect is the reason why glucose entering the blood from the digestive tract causes a more significant increase in the insulin content in the blood compared to the same amount of glucose, but administered intravenously. Incretins are a group of hormones and this effect is caused by two incretin hormones called glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).These hormones are released from enteroendocrine cells that are located in the walls of gut when nutrients enter the bowel. So 70-80% of insulin secretion by oral glucose induced insulin secretion from beta cells of pancreas is a result of insulinotropic effect of incretin hormones.

1)The molecules involved in regulating the secretion of insulin by the beta cells of the pancreas are Glucose,calcium,amino acids like arginine and leucine, acetylcholine, sulfonylurea, cholecystokinin, incretins like GLP-1 and GIP.

2)Synthesis of insulin is in beta cells of pancreas. The gene of insulin is transcribed into mRNA and then translated into preproinsulin.Its signal peptide is removed while insertion to Endoplasmic reticulum(ER) and forms proinsulin.It has an amino-terminal B chain, a carboxy-terminal A chain and a C peptide.Proinsulin is exposed to several endopeptidases in ER and is transported to Golgi apparatus where it is cleaved to yield insulin and C peptide.

Insulin is a protein that is secreted from beta cells in islets of Langerhans. When the blood glucose levels are elevated it also elevates the concentration of glucose in beta cells. Beta cells contains Glucose transporter 2 (GLUT2) to sense the glucose.As the glucose is transported to beta cells it leads to production of ATP resulting in increased ATP/ADP ratio. This closes the K+ channels and it causes depolarization of cell membrane. Calcium channels in cell membrane opens and allows calcium flow that triggers extrusion of insulin containing secretory granules thus resulting in insulin secretion.

The glucose is important in this because beta cells uses glycolysis mechanism when glucose concentration is elevated in blood.This metabolism of glucose produces ATP resulting in increased ATP/ADP ratio and insulin secretion.

3)The Glucagon like peptide (GLP-1) receptor is a receptor in beta cells of pancreas.It has two domains one is Extracellular domain that binds to C terminal helix od GLP 1 and another is transmembrane domain that binds to N terminal region of GLP1.This receptor works with canonical-seven transmembrane(7TM) helical domain.

4)The incretin hormons GIP and GLP1 is secreted by K cells from upper small intestine and enteroendocrine in distal intestine simultaneously.These secretions are regulated with the glucose intake .It is directly dependant in this glucose intake and rapidly secretes insulin.This is incretin effect.As this is directly related to glucose it acts immediately other than the main activators of insulin secretion.This is the reason why people with type 2 diabetes shows low insulin production because this incretin effect is absent.