Lecture 10: Metabolic Homeostasis

Question 1

How much glucose does the brain require per day?

Answer 1

180g

Question 2

How is starvation related to exercise?

Answer 2

initial energy source: 80% fat (release of FFAs, breakdown of liver glycogen/protein)

Question 3

What does the metabolic switch entail in starvation state?

Answer 3

ketone bodies used as energy source - reduced reliance on glucose

Question 4

What are the 4 criteria for metabolic syndrome?

Answer 4

1) visceral obesity
2) insulin resistance
3) dyslipidemia
4) hypertension

Question 5

What is the primary hormone produced by WAT?

Answer 5

Leptin

Question 6

What are the 2 important transcription factors in WAT?

Answer 6

1) Sterol regulatory binding protein 1C (SREBP-1C)

2) PPARy

Question 7

What does SREBP-1C do?

Answer 7

1) promotes TG synthesis
2) increases glucokinase trapping glucose inside cells

(activated by lipids and insulin)

Question 8

What does PPARy do and what is its receptor?

Answer 8

regulates/promotes TG storage and adipocyte differentiation (lipids are the ligand)

INCREASES # of adipocytes

Question 9

How has PPARy been drugable to treat diabetes type 2?

Answer 9

agonists treat insulin resistance (promote TG storage but also makes more fat)

side effect is weight gain

Question 10

What is the class of PPARy agonists?

Answer 10

TZDs (thiazolidinediones)

Question 11

as leptin increases, what happens to fat?

Answer 11

increases (direct relationship)

Question 12

What are 2 hypothalamic hormone stimulators of appetite?

Answer 12

1) Neuropeptide Y

2) Agouti-related peptide

Question 13

What are 2 inhibitors of appetite?

Answer 13

1) aMSH (cleaved from POMC)

2) CART

Question 14

How does leptin affect appetite?

Answer 14

inhibits it!

Question 15

Why do obese people have high levels of leptin?

Answer 15

leptin resistant

Question 16

What leads to DM?

Answer 16

reduced production of insulin by pancreas (beta cell depletion/exhaustion)

Question 17

What happens to insulin receptors in hyperinsulinemia?

Answer 17

DOWNREGULATED

Question 18

What is the ultimate diagnosis of T2DM?

Answer 18

elevated HbA1c (>48mMol/l)

Question 19

What is HbA1c

Answer 19

a measure of glycosylated RBCs (too much glucose in the plasma, eventually starts to stick on RBCs)

Question 20

What is the fasting blood glucose in pre-diabetic patients?

Answer 20

100-125mg/dl

Question 21

What is the oral glucose tolerance test?

Answer 21

8 hour fast, measure glucose before and 2h after consumption of 75g glucose

Question 22

What does C-peptide tell you?

Answer 22

indication of how well the pancreas is working

Question 23

What are 3 symptoms of T2DM?

Answer 23

1) Polyphagia (cellular starvation)
2) Polyuria (excess glucose in blood leads to increased plasma osmolarity pulling H2O)
3) Polydipsia (severe dehydration)

Question 24

How do Sulfonylurea drugs help T2DM patients?

Answer 24

stimulate insulin release (close ATP dependent K+ channels)

Question 25

What are examples of sulfonylureas?

Answer 25

glipizide | glyburide

Question 26

What does metformin do?

Answer 26

inhibits hepatic gluconeogenesis | increases insulin receptor activity

Question 27

What do alpha glucosidase inhibitors like precose or glyset do?

Answer 27

delay intestinal absorption of carbs

Question 28

What are some leading theories behind beta cell dsyfunction?

Answer 28

1) islet amyloid buildup 2) ER stress 3) lipotoxicity

Question 29

Ketoacidosis characterizes which type of diabetes?

Answer 29

1 (in the absence of insulin therapy)

Question 30

How does ketoacidosis occur in T1DM?

Answer 30

increase FFA release (hepatic precursor for ketone acids) ----> metabolism of ketone bodies for energy ----> increased blood acidity ----> diabetic coma/severe dehydration

Question 31

What is the main difference between absolute and relative insulin deficiency?

Answer 31

Absolute: lipolysis (increases ketogenesis)

Question 32

How is mental acuity related to blood sugar?

Answer 32

increase blood sugar, increase blood osmolarity (dehydrates) | alert (320mOsm) drowsy (330) stupor (340) coma (360)

Question 33

How are GH and insulin related?

Answer 33

AA from protein stimulates GH which stimulates IGF-1 IGF-1 simulates glucose uptake in muscle, proliferation of visceral organ tissues, inhibits proteolysis GH opposes insulin lipogenesis

Question 34

is GH high or low in times of starvation?

Answer 34

HIGH (increased AA from proteolysis stimulates it) but no IGF-1 (no insulin) so no negative feedback on GH

Question 35

List the physiological hallmarks of starvation

Answer 35

1) No insulin, low glucose 2) catecholamines stimulate glucagon 3) GH increases (increase AA due to proteolysis) 4) no negative feedback on GH (no IGF-1) 5) Cortisol (stress) increases

Question 36

What is the most highly associated genetic polymorphism in T2DM?

Answer 36

TCF72 (part of Wnt signaling) participates in islet cell development

Question 37

When does islet neogenesis occur?

Answer 37

embryonic development (beta cell replication continues during childhood but is stable in adults)