Body Mass Diabetes

Question 1

Does hexokinase 4 have a high or low affinity for glucose? What about hexokinase 1?

Answer 1

Hexokinase 4: low affinity (Liver doesn’t use glucose until it is very high in [])

Hexokinase 1: high affinity

Question 2

What does post-prandial mean?

Answer 2

post food intake

Question 3

What happens to glucose levels immediately after a meal? What is secreted as a result? What two glycolytic pathways become activated?

Answer 3

Glucose levels increase

Insulin is secreted: glycolysis and glycogenesis increase

Question 4

What happens to glucose levels 2 hours post-prandial? What is secreted as a result?

Answer 4

Glucose levels begin to drop.

Glucagon is secreted

Question 5

What is secreted 4 hours post-prandial?

Answer 5

more glucagon

Question 6

What becomes a major fuel 4 hours post prandial? What is being hydrolized?

Answer 6

FA - more TGA hydrolysis

Question 7

During prolonged fasting, what does the body start to break down? For what purpose?

Answer 7

The liver breaks down non-essential (glucogenic!) AAs to provide fuel to the brain

Question 8

What 2 reactions do the non-essential AAs degraded by the liver undergo? What does this break the AAs into?

Answer 8

Transimation and deamination reactions

Carbon skeleton + NH3(+)

Question 9

What happens to the extra amino groups of the non-essential AAs after undergoing transamination/deamination reactions?

Answer 9

Converted to urea, which is exported via the bloodstream to the kidneys and excreted in the urine

Question 10

What are the carbon skeletons of the non-essential glucogenic amino acids converted to? What does this lead to?

Answer 10

Pyruvate or intermediates of the TCA cycle. This leads to gluconeogenesis in the liver

Question 11

What does gluconeogenesis yield?

Answer 11

Glucose for export to the BRAIN!!!

Question 12

Where do FAs come from that are imported into the liver?

Answer 12

Adipose tissue

Question 13

What happens to FAs that enter the liver from adipose tissue?

Answer 13

They are oxidized as fuel, producing acetyl-CoA

Question 14

Why is the acetyl-CoA that was produced from FAs unable to enter the TCA cycle? What happens to acetyl-CoA?

Answer 14

because oxaloacetate is constantly being depleted by the use of the TCA cycle intermediates for gluconeogenesis. Acetyl-CoA accumulates!

Question 15

What does the accumulation of acetyl-CoA in the liver favor the formation of?

Answer 15

Acetoacetyl-CoA + ketone bodies

Question 16

What happens to the ketone bodies formed via the accumulation of acetyl-CoA in the liver? What happens to the excess ketone bodies?

Answer 16

They are exported to the brain via the bloodstream. Brain uses them as fuel. The excess end up in the urine

Question 17

What is necessary for starvation?

Answer 17

The accumulation of fat

Question 18

Proteins containing what sequence are preferably depleted in the liver and heart?

Answer 18

Lys-Phe-Glu-Arg-Gln

Question 19

In terms of fuel reserves in the body, what is the main difference between obese and normal weight people?

Answer 19

Adipose tissue.

Extra fat = extra fuel…but also means increased inflammation, electrolyte imbalance, etc.

Question 20

How many days can one survive on a hunger strike?

Answer 20

30-40 days IF HYDRATED

Question 21

When on a hunger strike, when do severe symptoms begin to appear? Examples?

Answer 21

35-40 days (hallucinations, seizures, susceptible to infection, etc.)

Question 22

People that are starving die of what?

Answer 22

Infection, not lack of nutrients by itself

Question 23

What is type 1 diabetes? What is the cause? When does it develop?

Answer 23

Insufficient production of insulin.

Cause: Autoimmune destruction of beta-cells

Early in life - childhood

Question 24

What is type 2 diabetes? When does it develop? How do cells interact with insulin?

Answer 24

Insulin resistance.
Also associated with reduced insulin because beta-cells eventually give up.

Develops in late adulthood

Cells don’t respond appropriately to insulin

Question 25

In which type of diabetes is blood glucose elevated?

Answer 25

Both types

Question 26

What do people that have diabetes do a lot?

Answer 26

Pee a lot and drink lots of water - always thirsty (increased osmolality)

Question 27

Osmolality of blood increases with what?

Answer 27

Dehydration

Question 28

What happens to proteins in diabetes?

Answer 28

They get glycosylated: become abnormally functional

Question 29

In type 1 and advanced type 2 diabetes, what accelerates? What does this lead to?

Answer 29

Fat breakdown accelerates --> ketone bodies

Question 30

In type 1 diabetes, what does raised blood [proton] lead to?

Answer 30

ketoacidosis

Question 31

In type 1 diabetes, what does the activation of the bicarbonate buffering system lead to?

Answer 31

altered breathing pattern

Question 32

In type 1 diabetes, what does the breakdown of ketone body acetoacetate produce? How is it expelled? What does this cause behaviorally?

Answer 32

Acetone which is expelled via breaths Causes slow and deep breaths

Question 33

What does untreated diabetes lead to?

Answer 33

dramatic weight loss

Question 34

Adipose tissue is also what?

Answer 34

An endocrine organ

Question 35

What do adipose tissues release?

Answer 35

Peptide hormones called adipokines.

Question 36

What is the function of adipokines that are released from adipose tissue?

Answer 36

Carry information about fuel stores to the brain - signal to the brain to control appetite and food intake

Question 37

What are two examples of adipokines?

Answer 37

Leptin | Adiponectin

Question 38

What hormone do anorexogenic neurosecretory cells carry? What message does this hormone carry to neurons in the hypothalamus?

Answer 38

alpha-MSH "Eat less, metabolize more"

Question 39

What hormone do orexogenic neurosecretory cells carry? What message does this hormone carry to neurons in the hypothalamus?

Answer 39

NYP "Eat more, metabolize less"

Question 40

What hormone(s) activate the release of alpha-MSH from anorexogenic neurosecretory cells?

Answer 40

Leptin (secreted from adipose)

Question 41

What hormone(s) activate the release of NPY from orexogenic neurosecretory cells?

Answer 41

Ghrelin (secreted from stomach)

Question 42

What hormone(s) inhibit the release of NPY from orexogenic neurosecretory cells?

Answer 42

Leptin (secreted from adipose) PYY(36-6) & GLP-1 (secreted from gut) Insulin (secreted from pancreas)

Question 43

Once the neurosecretory cells in the hypothalamus receive hormonal input, where do they relay the signals to?

Answer 43

To cells of muscle, adipose tissue, and liver/.

Question 44

What does the leptin hormone do?

Answer 44

It reduces appetite

Question 45

Where was the leptin gene first identified? What was the behavior of ob/ob mice?

Answer 45

Obese mice. Ate continually, obese, elevated cortisol (stress hormone), shivered (uncontrollable body weight), infertile, insulin resistance, died early.

Question 46

What happened to the obese mice when leptin was injected into their body?

Answer 46

The mice lost weight & body temp returned to normal.

Question 47

How does the injection of leptin affect obese people?

Answer 47

They do not lose weight, do not restore normal body mass

Question 48

What does the db gene encode?

Answer 48

It encodes the leptin receptor (Lepr) in the brain (mainly in hypothalamus?)

Question 49

How can the db/db mice be characterized?

Answer 49

obese and diabetic

Question 50

What is Ghrelin?

Answer 50

A short-term orexigenic peptide that is secreted from the stomach.

Question 51

Where can ghrelin receptors be found?

Answer 51

Brain, heart, adipose tissue

Question 52

What receptor/signaling pathway does Ghrelin bind to? Purpose?

Answer 52

GPCP Purpose: to increase the sensation of hunger

Question 53

What happens immediately after the injection of ghrelin in the body?

Answer 53

Increased appetite

Question 54

How can the PYY hormone be characterized?

Answer 54

Appetite suppressing. "Eat less, metabolize more"

Question 55

How many AAs does the PYY peptide contain? It has __ _____ residues at the end.

Answer 55

36 AA 2 tyrosine

Question 56

Where is PYY secreted from?

Answer 56

Small intestine, colon

Question 57

What does PYY inhibit? What does this result in?

Answer 57

The release of orexigenic NYP neurons. Result: reduced hunger

Question 58

What affects gut microflora?

Answer 58

Diet. Obese and lean people have different gut microflora.

Question 59

What do some microorganisms create that affects adipose tissue?

Answer 59

Fermentation products

Question 60

What are the majority of bacterial products? Give 3 examples

Answer 60

Short-chain FA. 1. acetate 2. propionate 3. butyrate

Question 61

What receptor does propionate act through?

Answer 61

GPCR 43 & 41

Question 62

What does propionate stimulate? What does it inhibit?

Answer 62

Stimulates adipocyte differentiation Inhibits lipolysis

Question 63

In an individual with a healthy body mass, what does TAG uptake from diet = ?

Answer 63

= TAG catabolized

Question 64

In overweight individuals, what does excess caloric intake result in?

Answer 64

Enlarged adipocytes, overloaded with TAGs and unable to store more

Question 65

What do enlarged adipocytes secrete? What does this attract?

Answer 65

MCP-1 which attracts macrophages

Question 66

What do the macrophages that were attracted to adipose tissue due to the secretion of MCP-1 do?

Answer 66

They take over the adipose tissue and produce TNF-alpha (tumor necrosis factor).

Question 67

What does TNF-alpha favor?

Answer 67

It favors the export of fatty acids from adipocytes to muscle.

Question 68

What happens as FAs are exported from adipocytes to muscle?

Answer 68

Ectopic (small) lipid deposits form in muscles.

Question 69

What do ectopic lipid droplets in the muscle interfere with?

Answer 69

Interferes with GLUT4 movement to the myocyte surface...this causes insuline resistance.

Question 70

What is one held belief about insulin resistance due to TAG overload?

Answer 70

Insulin resistance leads to obesity. But I believe that....obesity leads to insulin resistance.