Pancreatic Peptide Hormones Flashcards
What are the islets of Langerhans, what % of the organ do they constitute, what are the main cell types in the islets and what do they secrete?
Islets of Langerhans make up 1-2% of weight of pancreas, play a pivotal role in metabolic homeostasis, and contain 4 major types of cells. Alpha cells secrete glucagon, Beta cells secrete insulin, D cells secrete somatostatin and F cells secrete pancreatic peptide.
Briefly describe the structure of insulin.
Insulin has a heterodimeric structure having an A chain 21 amino acids long, and a B chain 30 long. A and B chains held together by 2 disulfide bonds with a third within the A chain.
Briefly, what reactions take place between the synthesis of preproinsulin to the final cleavage in the secretory granules? Where are the contents of the granules released?
Preproinsulin has a signal peptide sequence of 23 amino acids that is removed, forming proinsulin. Proinsulin is folded and disulfide bridges are made. It is then packaged into secretory granules where it forms a complex with Zn. Contents of secretory granules are released into portal circulation.
Comment briefly on the magnitude of the effects that insulin has on cells. Name 3 enzyme activities that are increased and 3 that are decreased by the action of insulin.
Insulin generally has anabolic effects, producing fuel storage, growth and modification of many tissue functions. Also, stimulates transport of glucose into cells, except brain, liver and erythrocytes. 3 that are increased are glucokinase, phosphofructokinase and HMG-CoA reductase. 3 that are decreased are glucose-6-phosphatase, fructose-I,6-bisphosphatase and PEP carboxykinase.
Very briefly describe the location and structure of the insulin receptor. What reaction does it perform upon itself when insulin binds? What cells are not stimulated by insulin to transport glucose?
Insulin receptor is heterotetrameric, made up of 2 Alpha and 2 Beta chains (Alpha are outside the plasma membrane and Beta extend from cytoplasm through plasma membrane). When insulin binds to the receptor, autophosphorylation of the Beta chains takes place by a protein tyrosine kinase reaction. Cells of the liver, brain and erythrocytes are not stimulated by insulin to transport glucose.
- In terms of insulin receptors, what is “down regulation”? In what circumstances are cells “up regulated”? Is the glucose transporter the same or different than the insulin receptor?
When insulin binds to an insulin receptor, the entire complex is internalized into the cytoplasm of the cell. This makes the cell less responsive to further insulin challenges = “down regulation”. If a cell has not been recently exposed to insulin, then it has an increased number of insulin receptors on its surface, known as “up regulation”. Once the insulin/receptor complex is formed a distinctly different glucose transporter is translocated to the plasma membrane increasing the amount of glucose entering the cell.
What is the effect that glucagon has on insulin secretion and vice versa? What general types of effects does glucagon have?
Insulin suppresses glucagon secretion and glucagon stimulates insulin release. Glucagon is essentially an insulin antagonist that generally has catabolic effects which cause the breakdown and usage of energy stores.
What is the general type of receptor used with glucagon? Give a very brief description of the structure of glucagon.
Glucagon uses an independent glucagons receptor on the plasma membrane. Glucagon is a 29 amino acids polypeptide which is synthesized in the a cells of the islets of Langerhans.
What are 2 locations where somatostatin is secreted? What is the function of somatostatin? What is somatostatin used for clinically?
Somatostatin is secreted mainly be the D cells of the islets of Langerhans as well as the hypothalamus. It inhibits the secretion of insulin and glucagons as well as growth hormone. It also decreases the amount of pancreatic digestive enzyme available. Used clinically to treat hemorrhaging in the pancreas and GIT, to prevent acromegaly and to prevent pancreatitis.
