Flashcards in Week 4 Insulin/Glucagon Structure Synthesis Lecture Deck (22):
what are the endocrine and exocrine portions of the pancreas called?
Endocrine: islets of langerhan
Exocrine: compound acinar gland
what are the cell types within the islets of langerhan? what do they produce? what cell type is the mos abundant?
alpha cells: secrete glucagon
beta cells: secrete insulin (most abundant cell type in islets of langerhan)
delta cells: secrete somatostatin
Insulin: produced by? produced when? fxn?
beta cells, when blood glucose is elevated, stimulates glucose uptake in skeletal muscle and adipocytes
Type I diabetes caused by?
lack of insulin production
Type II diabetes caused by
lack of insulin receptors
Insulin binds what type of receptor?
what effect does insulin binding RTK have?
activates PI-3K and stimulates vesicles containing GLUT4 (in their memrbane) to fuse with plasma membrane
GLUT4 role? found?
the only insulin sensitive glucose transporter. allows glucose to enter the cell. found in muscle cells (skeletal and cardiac) and adipocytes
what is the structure of mature insulin?
A and B chain linked together by 2 disulfide bonds with a third disulfide bond within the A chain
describe the formation of mature insulin:
1. preproinsulin is translated (contains signal peptide, B chain, C chain and A chain)
2. as preproinsulin is translated the signal peptide signals it to move to the rER.
3. singnal peptide is cleaved by signal peptidases to form pro-insulin (inside rER)
4. Pro-insulin (B, C, A chains) folds and form disulfide bonds in rER
5. Final processing (cutting of B from A occurs after proinsulin passes through golgi and into secretory vesicles. cleavage occurs via prohormone convertases
6. cleavage produces equimolar mature insulin and C peptide (secreted together)
compare stability of C peptide to that a mature insulin. significance?
C peptide is much more stable than insulin (3-8 min half life). this allows C-peptide to be used to determine how much insulin the pancreas is producing
A and B chains of insulin have what secondary structure?
what is the storage form of insulin within secretory vesicles?
dimers of insulin (ab/ab) arrange in a 3-fold symmetry (6 ab or 3 ab/ab dimers) around a Zn ion
when does insulin regain its "normal" ab form?
after it is secreted from the vesicles
what is the benefit to having insulin storage form?
condenses insulin and allows more to be carried within each vesicle
each pancreatic islet of langerhan is vascularized, why?
allows islets to respond quickly to blood glucose levels and also rapidly transport insulin
what are the steps in insulin secretion?
1. Glucose is transported into beta cells via GLUT2 *glucose sensor
2. Glycolysis and ATP increase within the beta cell
3. increased ATP closes K channels
4. Membrane potential changes and voltage gated Ca channels open
5. calcium triggers release of insulin containing vesicles
what is meant by biphasic insulin secretion?
upon glucose stimulation two "waves" of insulin release occur. The initial burst and then a more prolonged release
what accounts for biphasic insulin secretion?
some insulin vesicles are ready and docked within a Beta cell and are released faster. other vesicles are deeper within the cell and take a little extra time to be released
what is the role of glucagon?
increase or maintain glucose levels
structure of glucagon
simple alpha helical structure