Wk2 Mech and Gen of Diabetes

Question 1

HNF-4a

Answer 1

MODY 1

Question 2

glucokinase mutation

Answer 2

MODY 2

Question 3

PDX1

Answer 3

MODY 4

Question 4

Predominant gene polymorphisms in DM1:

Answer 4

MHC II

Question 5

DM2: chronic inflammation of adipose tissue, 3 stages:

Answer 5

1. increase in size
2. MCP-1 secretion by adipocytes
3. Macs secrete TNFa –> inflammation

Question 6

TNFa role in DM2 in adipocytes:

Answer 6

inhibits TG synthesis in favor of free FA formation by inhibiting PPARY

Question 7

Free FA role in DM2 in adipocytes:

Answer 7

bind TLR –> NFKB/JNK –> inactivates IRS –> inhibits insulin signaling pathway –> insulin resistance

Question 8

Two pathways to insulin resistance in skeletal muscle:

Answer 8

1. TLR pathway

2. Diacylglycerol pathway

Question 9

Steps in DAG pathway to insulin resistance:

Answer 9

increased FAs –> increased DAG –> + PKC –> inhibits IRS

Question 10

IRS?

Answer 10

Insulin receptor signaling

• promotes vesicular trafficking of GLUT4 to cell surface

Question 11

Two insulin resistance pathways in hepatocytes:

Answer 11

1. TLR

2. DAG

Question 12

What is different about glucose uptake in the liver?

Answer 12

GLUT2 instead of GLUT4

**GLUT2 is not insulin dependant

Question 13

Result of insulin resistance in the liver:

Answer 13

1. decreased glycogen synthesis

2. GREATLY increased gluconeogenesis – main contributor to hyperglycemia in DM2

Question 14

Final step in DM2 at the level of pancreas?

Answer 14

Destruction of beta cells due to inflammation

Question 15

Two ways pancreatic beta cells die in DM2:

Answer 15

1. oxidative stress

2. ER stress – UPR (unfolded protein response)

Question 16

UPR?

Answer 16

unfolded protein response in beta cell ER –> apoptosis