Block 3 Lecture 4 -- Hormonal Regulation of Fuel Metabolism

Question 1

What tissue-specific hormone receptors are present in the liver?

Answer 1

1) GLUT-1
2) alpha-adrenergic
3) beta-adrenergic
4) glucagon

Question 2

What tissue-specific hormone receptors are present in the muscle?

Answer 2

1) GLUT-4
2) beta-adrenergic
3) insulin

Question 3

Typical FPG?

Answer 3

80-100 mg/dL

Question 4

Typical post-prandial [glucose]?

Answer 4

120-140 mg/dL

Question 5

MW of glucose?

Answer 5

180 g/mol

Question 6

What happens if glucose < 80 mg/dL?

Answer 6

coma, death, hemolysis

Question 7

What are the consequences of not storing fat?

Answer 7

1) atherosclerosis, LDL = stroke, MI

Question 8

What happens if too much fat is stored?

Answer 8

fat-only catabolism

Question 9

What are the functions of insulin?

Answer 9

1) promotes nutrient storage
2) anabolic for blood proteins
3) promotes utilization of glucose for fuel

Question 10

What are insulin’s nutrient storage effects?

Answer 10

1) glycogen synthesis
2) protein synthesis
3) TG synthesis in liver
4) TG storage in adipose

Question 11

How is insulin sotred?

Answer 11

as the Zn2+ complex

Question 12

Describe the structure of insulin?

Answer 12

2 peptide chains connected by 2 disulfides

Question 13

What is structure of proinsulin?

Answer 13

folded with formation of disulfide bonds

Question 14

Structure of pre-proinsulin

Answer 14

translation product after processing removes signal sequence in the RER

Question 15

Why is C-peptide a good diagnostic tool?

Answer 15

not cleared as rapidly as insulin

Question 16

What factors stimulate insulin release?

Answer 16

1) parasympathetic stimulation
2) Ala/Arg
3) GIP

Question 17

What factors inhibit insulin release?

Answer 17

insulin

Question 18

How is insulin solubilized from its storage form?

Answer 18

Ca++ displaces Zn++

Question 19

What stimulates glucagon release?

Answer 19

1) catecholamines
2) cortisol
3) GI hormones
4) AAs

Question 20

What control glucagon release?

Answer 20

lack of insulin

Question 21

What suppresses glucagon release?

Answer 21

insulin and glucose

Question 22

half-life of glucagon?

Answer 22

4 minutes

Question 23

functions of glucagon?

Answer 23

1) stimulates glycogenolysis and gluconeogenesis in liver

2) mobilizes FAs in adipose

Question 24

What other factors affect glucagon release?

Answer 24

1) blood metabolite levels
2) neuronal signals
3) other insulin opponents

Question 25

What percentage of islet is beta cells?

Answer 25

75%

Question 26

What percentage of islet is alpha cells?

Answer 26

20%

Question 27

What percent of islet is delta cells?

Answer 27

5%

Question 28

What does the cholera toxin do?

Answer 28

inhibits GTP hydrolysis by Galpha

Question 29

What is the reaction catalyzed by adenylate cyclase?

Answer 29

4 ATP --> 4 AMP --> 4 cAMP

Question 30

What is the function of phosphodiesterase?

Answer 30

inactivates cAMP

Question 31

What substances inhibit PDE?

Answer 31

caffeine, theophylline, theobromine

Question 32

What does cAMP do?

Answer 32

binds regulatory dimer of PKA to allow catalytic dimer to phosphorylate shit

Question 33

What is a CRE?

Answer 33

cAMP Response Element, a DNA promoter that encodes gluconeogenesis enzymes

Question 34

How are CRE's bound to stimulate transcription?

Answer 34

cAMP-PKA phosphorylates CREBs that then bind CREs

Question 35

What hormones function through membrane receptors?

Answer 35

1) glucagon 2) epinephrine 3) beta-receptors

Question 36

What hormones function through RTKs?

Answer 36

insulin

Question 37

Describe RTK action?

Answer 37

1) dimerizes | 2) TK autophosphorylates Tyr residues

Question 38

What hormones function through PIP2 hydrolysis couplers?

Answer 38

epinephrine alpha receptors

Question 39

What hormones function through gated ion channels?

Answer 39

1) angII | 2) neurotransmitters

Question 40

What do alpha1 receptors do?

Answer 40

vascular smooth muscle contraction via PIP2

Question 41

What do beta1 receptors do?

Answer 41

myocardial increase HR & contractility

Question 42

What do beta2 and 3 receptors do?

Answer 42

fuel metabolism

Question 43

How does the insulin RTK take effect?

Answer 43

IRS (insulin receptor substrate) has an SH2 domain that binds Tyr-PO4s of RTK

Question 44

What does IRS-1 do?

Answer 44

affects glucose metabolism

Question 45

What does IRS-2 do?

Answer 45

affects fat metabolism

Question 46

What are cortisol's effects?

Answer 46

works synergistically with glucagon to... | 1) mediate long-term changes in fuel metabolism

Question 47

What is the MoA of sulfonylureas?

Answer 47

blocks ATP-dependent K+ channels in beta cells to increase Ca++ mobilization

Question 48

What are the sulfonylureas?

Answer 48

1st gen: tolbutamide | 2nd gen: glipizide, glimepiride, glibencalmide

Question 49

What is the MoA of repaglinide?

Answer 49

same as Sulfonylureas

Question 50

What is the MoA of metformin?

Answer 50

stimulates AMP-activated PK to decrease liver gluconeogenesis via expression of SHP which inhibits expression of PEPCK & G6Pase

Question 51

What class of hypoglycemic agents is Metformin from?

Answer 51

biguanide

Question 52

Where is metformin derived from?

Answer 52

french lilac

Question 53

What is salsalate's mechanism of action?

Answer 53

NSAID with blood-sugar lowering activity, decreases inflammation, increases insulin sensitivity

Question 54

What drugs are DPP4 inhibitors?

Answer 54

sitagliptin, saxagliptin

Question 55

What is the MoA of DPP4-inhibitors?

Answer 55

inhibits dipeptidylpeptidase-4 (involved in glucagon release); also stimulate insulin release by inhibiting inactivation of insulin-stimulating incretins

Question 56

What is the MoA of exantide?

Answer 56

incretin mimetic

Question 57

What is the MoA of Liraglutide?

Answer 57

GLP-1 analog with palmitate side chain that acts like incretins

Question 58

How is synthetic glucagon administered?

Answer 58

IM or SQ