L6

Question 1

Which subunit of the insulin receptor does insulin bind to?
A. alpha
b. beta

Answer 1

A. alpha

Question 2

True or False: The alpha subunit of the insulin receptor has tyrosine kinase activity and receptor autophosphorylation

Answer 2

False - beta subunit

Question 3

In the insulin receptor, phosphorylation of insulin receptor substrate (IRS) proteins leads to activation of PI3K/MAPk, as well as ___trafficking

Answer 3

GLUT-4

Question 4

____: the principal effector of the PI3K pathway

Answer 4

AKT

Question 5

True or False: In the insulin receptor, the cytoplasmic protein CBL is the DIRECT phosphorylation target

Answer 5

True

Question 6

True or False: Skeletal muscle glucose uptake is increased in T2DM

Answer 6

False - skeletal muscle glucose uptake is REDUCED in T2DM

Question 7

Impaired insulin receptor signaling is a result of: ____ cytokines, which is mediated by activation of _____ receptors

Answer 7

intracellular; TLR

Question 8

Impaired insulin receptor signaling is a result of: ____ cytokines, which is mediated by ____ (such as: TNF-a)

Answer 8

extracellular; adipokines

Question 9

Excessive oxidation of free fatty acids is just one mechanism of skeletal muscle insulin resistance. Which two locations do FFA’s come from?

Answer 9

1) Visceral adipose tissue
2) Intracellular lipid storage

Question 10

True or False: Mitochondrial dysfunction and modulation of gene transcription are mechanisms of skeletal muscle insulin resistance

Answer 10

True

Question 11

What two sources can activate TLR’s?
A. Bacterial products in plasma (e.g LPS)
B. Antibiotics
C. Cytokines
D. Systemic FFA’s

Answer 11

A/D

Question 12

True or False: Obesity alters intestinal bacterial composition

Answer 12

True

Question 13

True or False: Leaky gut does NOT allow entry into systemic circulation

Answer 13

False - leaky gut ALLOWS entry into systemic circulation

Question 14

Activation of TLR leads to intracellular production of ___ (leads to inflammatory gene expression) and ___

Answer 14

NF-kB; MAPK

Question 15

TLR activation generates intracellular cytokines, such as _____

Answer 15

TNF-a

Question 16

TLR activation leads to interruption of insulin receptor signaling via: phosphorylation of ____

Answer 16

IRS (insulin receptor substrate)

Question 17

True or False: Systemic fatty acids activate TLR (e.g TLR4)

Answer 17

True

Question 18

Binding of FA to TLR4 leads to activation of ____, which activates NF-kB and MAPK.

A. TNF
B. IL-6
C. proIL-1B
D. MD2
E. MyD88

Answer 18

E. MyD88

Question 19

True or False: Activation of NF-kB leads to activation of TNF, IL-6, proIL-1B, and proIL-18

Answer 19

True

Question 20

True or False: Bacterial products (LPS) lead to activation of TLR, which leads to production of cytokines and inhibition of insulin signaling

Answer 20

True

Question 21

____ KO mice are protected from diet induced obesity (DIO)
A. TLR4
B. MyD88
C. NF-kB
D. MAPK

Answer 21

B. MyD88

Question 22

Activation of TLR leads to activation of ___ kinases
A. glutamate
B. glycine
C. serine
D. tryptophan
E. tyrosine

Answer 22

C. serine

Question 23

Phosphorylation of serine residues INHIBITS function of insulin receptor and prevents ___ kinase from phosphorylating IRS proteins
A. glutamate
B. glycine
C. serine
D. tryptophan
E. tyrosine

Answer 23

E. tyrosine

Question 24

How does TNF-alpha (extracellularcytokine) affect tyrosine kinase activity?

Answer 24

Decrease it
- Thereby: block fx of insulin receptor

Question 25

True or False: Visceral adipose tissue has a low lipolytic activity

Answer 25

False - it has a HIGH lipolytic activity

Question 26

Insulin resistance ____ lipid accumulation in adipocytes A. limits B. exceeds

Answer 26

A. limits

Question 27

True or Fales: excess storage capacity of adipocytes (obesity) leads to increased in lipid storage in other organs (e.g - liver, skeletal m., pancreatic islets)

Answer 27

True

Question 28

There is a higher density of which type of receptor, in visceral adipose tissue, that contributes to its higher lipolytic activity?

Answer 28

High density of adrenergic receptors (B2 on adipocytes is activated by NE/EPI)

Question 29

True or False: In visceral adipose tissue, the isoform of lipase IS effectively inhibited by insulin

Answer 29

False - it is NOT

Question 30

Visceral adipose tissue has high ___ activity A. HSD11B2 B. HSD11B1 C. CYP21 What is the effect?

Answer 30

B. HSD11B1 (converts cortisone to cortisol) - Leads to increased local cortisol production (lipolysis)

Question 31

How does hormone sensitive lipase (HSL) leads to hyperlipidemia (increased FFA in the blood)?

Answer 31

Lipolysis

Question 32

True or False: Unhealthy adipose expansion and inflammation leads to lipotoxicity and ectopic lipid deposition

Answer 32

True

Question 33

High: cell hypertrophy, inflammation, macrophage infiltration Low: adipogenesis and insulin sensitivity A. Healthy expansion B. Unhealthy expansion

Answer 33

B. Unhealthy expansion

Question 34

How does excessive fatty acyl-CoA beta oxidation affect glycolysis and glucose entry? intermediates?

Answer 34

1) Limits it 2) Increased intermediates (e.g DAG, ceramides)

Question 35

Diacylglycerol (DAG) activates ___, which blocks ___ through ____ phosphorylation

Answer 35

PKC; IRS-1; serine

Question 36

DAG activates ____, leading to inflammatory response and insulin resistance

Answer 36

Diacylglycerol kinase (DGK)

Question 37

Increased fat oxidation in muscle leads to an increased in intermediates, such as: ___

Answer 37

DAG

Question 38

What are the four main outcomes of excessive FFA oxidation?

Answer 38

1) Excessive generation of fatty acyl CoA 2) Accumulation of DAG 3) Activation of serine kinase (protein kinase C) 4) Serine phosphorylation of IRS proteins

Question 39

What can drive mitochondrial dysfunction?

Answer 39

Chronically elevated plasma lipids

Question 40

Dysfunction of which organelle can lead to increased generation of ROS by that very organelle?

Answer 40

Mitochondria

Question 41

What are two effects of chronically elevated plasma lipids?

Answer 41

1) Make intracellular cytokines via TLR's 2) Excess FFA B-oxidation

Question 42

True or False: Mitochondrial dysfunction does not harm proteins, lipids, nucleic acids

Answer 42

False - mitochondrial dysfunction DOES damage protein, lipids, and nucleic acids

Question 43

How does mitochondrial dysfunction affect: - # of mitochondria - mitochondrial function - oxidative capacity - GLUT4 transcription

Answer 43

Decreases all of the above

Question 44

How can impaired mitochondrial function decreased insulin response?

Answer 44

Activates MAPK/NF-kB, increase IRS1 phosphorylation of serine and decrease phosphorylation of tyrosine

Question 45

True or False: When there is impaired mitochondrial function, both increase in FFA derivatives and ROS can lead to activation of MAPK and NF-kB

Answer 45

True

Question 46

How does mitochondrial dysfunction affect IRS proteins?

Answer 46

Leads to their nitrosylation and degradation

Question 47

What are four characteristics of beta cell dysfunction?

Answer 47

1) Altered pattern of insulin secretion 2) Decreased sensitivity to glucose 3) Reduced processing of proinsulin 4) Hyperglycemia induced changes in gene expression

Question 48

True or False: Improved glucose clearance and increased sensitivity to glucose are features of dysfunctional pancreatic beta cel

Answer 48

False - IMPAIRED glucose clearance and DECREASED sensitivity to glucose