Week 4 Insulin/Glucagon Structure Synthesis Lecture

Question 1

what are the endocrine and exocrine portions of the pancreas called?

Answer 1

Endocrine: islets of langerhan
Exocrine: compound acinar gland

Question 2

what are the cell types within the islets of langerhan? what do they produce? what cell type is the mos abundant?

Answer 2

alpha cells: secrete glucagon
beta cells: secrete insulin (most abundant cell type in islets of langerhan)
delta cells: secrete somatostatin

Question 3

Insulin: produced by? produced when? fxn?

Answer 3

beta cells, when blood glucose is elevated, stimulates glucose uptake in skeletal muscle and adipocytes

Question 4

Type I diabetes caused by?

Answer 4

lack of insulin production

Question 5

Type II diabetes caused by

Answer 5

lack of insulin receptors

Question 6

Insulin binds what type of receptor?

Answer 6

RTK

Question 7

what effect does insulin binding RTK have?

Answer 7

activates PI-3K and stimulates vesicles containing GLUT4 (in their memrbane) to fuse with plasma membrane

Question 8

GLUT4 role? found?

Answer 8

the only insulin sensitive glucose transporter. allows glucose to enter the cell. found in muscle cells (skeletal and cardiac) and adipocytes

Question 9

what is the structure of mature insulin?

Answer 9

A and B chain linked together by 2 disulfide bonds with a third disulfide bond within the A chain

Question 10

describe the formation of mature insulin:

Answer 10

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)

Question 11

compare stability of C peptide to that a mature insulin. significance?

Answer 11

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

Question 12

A and B chains of insulin have what secondary structure?

Answer 12

alpha-helices

Question 13

what is the storage form of insulin within secretory vesicles?

Answer 13

dimers of insulin (ab/ab) arrange in a 3-fold symmetry (6 ab or 3 ab/ab dimers) around a Zn ion

Question 14

when does insulin regain its “normal” ab form?

Answer 14

after it is secreted from the vesicles

Question 15

what is the benefit to having insulin storage form?

Answer 15

condenses insulin and allows more to be carried within each vesicle

Question 16

each pancreatic islet of langerhan is vascularized, why?

Answer 16

allows islets to respond quickly to blood glucose levels and also rapidly transport insulin

Question 17

what are the steps in insulin secretion?

Answer 17

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

Question 18

what is meant by biphasic insulin secretion?

Answer 18

upon glucose stimulation two “waves” of insulin release occur. The initial burst and then a more prolonged release

Question 19

what accounts for biphasic insulin secretion?

Answer 19

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

Question 20

what is the role of glucagon?

Answer 20

increase or maintain glucose levels

Question 21

structure of glucagon

Answer 21

simple alpha helical structure

Question 22

describe the preprohormone of glucagon

Answer 22

translated in rER (like insulin), but contains peptides for several other hormones as well that are cleaved by prohormone convertases (different cleavage in different tissues)