Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Nutr 4210 > 11. Obesity (1) - insulin resistance > Flashcards

11. Obesity (1) - insulin resistance Flashcards

1
Q

Difference between peripheral and central obesity

A

Peripheral

  • subcutaneous fat
  • excess below the waist (hips, butt, thighs)
  • NOT likely a major health risk factor

Central (Abdominal) Obesity

  • visceral fat (surrounds heart, liver, intestines, kidney)
  • very strong predictor of health risk
  • pro-inflammatory, IR, diabetes risk, heart disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Easiest way to measure Visceral Fat

  • male and female measure
  • other ways to measure
A

waist circumference

  • men > 102 cm
  • women > 88 cm

others

  • MRI and CT
  • $$$
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

key independent predictor of all cause mortality

- some basic measurements

A

visceral fat

  • 0.5kg normal
  • 1.0kg 2 fold higher risk for mortality
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Why is increased visceral fat a potential health risk?

A

associated with

  • increased lipolysis
  • increased plasma FFAs
  • increased secretory products (adipokines -> inflammatory mediator)
  • *increased insulin resistance**
  • less glucose uptake into cells
  • increased blood glucose levels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what do adipokines do?

A

inflammatory mediator

adipo = fat
kines = signal molecules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is insulin resistance?

  • how does it impair normal response
  • result in skeletal muscle
A

inability of insulin to produce a “normal” response at a given tissue

  • defect in insulin signalling leads to impaired GLUT4 translocation to membrane
  • reduced insulin stimulated glucose uptake in muscle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

hyperinsulinemia definition

A
  • high levels of insulin in the blood

- result from over production of insulin in the pancreas in order to compensate for insulin resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

stages in the development of T2D

- is it reversible?

A

1) impaired glucose tolerance
- obesity causes insulin resistance and impaired glucose tolerance directly
- hyperinsulinemia -> over production of insulin to compensate for resistance

2) early diabetes
- decreased insulin secretion
- result from beta cell defect
- cells exhausted and damaged from overproduction

3) late diabetes
- beta cells fail
- no insulin produced

** can be reversible with lifestyle change depending on stage -> only lived with it for a few years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

clinal signs of T2D

A

Glucose
- fasting hyperglycemia (>7mM)

Insulin

  • dependent on stage of diabetes
  • impaired gluc tolerance -> high levels
  • early diabetes -> low levels
  • late diabetes -> no insulin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

clinical tests used to assess diabetes

A

1) oral glucose tolerance test

2) euglycemic / hyperinsulinemic clamp

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

diabetes NOT associated with diabetes

A

Type 1 diabetes
(aka juvenile or insulin-dependent diabetes)
- autoimmune disease
- children
- genetics or exposure to certain virusis
- no cure (irreversible)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

OGTT

A

Oral Glucose Tolerance Test
- measures acute metabolic response to glucose ingestion at whole body level

Method

  • 75g glucose beverage (Trutol)
  • measured 2hrs after ingestion (should return to near normal levels)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

OGTT clinical diagnostic measurements

A

Diagnostic criteria after 2hrs from ingestion

  • 7.8mM = impaired glucose tolerance
  • 11.1mM = T2D
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

OGTT response to “glucose” in lean, obese and T2D

A

Normal

  • fasting ~4-5mM
  • peak at 1hr ~6-7mM
  • return to normal after 2hr
  • obese without diabetes similar response*

T2D

  • impaired fasting glucose ~6-7mM
  • huge spike glucose response (peak at 1hr)
  • diagnosed with disease at 11.1mM after 2hr
  • > 3hrs to return to normal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

OGTT response to “insulin” in lean, obese and T2D

A

Fasting insulin - similar for all health states (~10mM but highly variable between individuals)

Lean (healthy)

  • peak after 30min ~40mM
  • slow/steady decline

Obese (healthy)

  • “huge”peak after 30min ~90mM (hyperinsulinemia)
  • indicates insulin resistance
  • pancreas works hard not to become diabetic

Obese T2D

  • peak after 1.5hr* (much longer)
  • peak response between obese and lean ~50-60mM
  • pancreas exhausted, fewer cells to secrete amount needed

Lean T2D

  • little to no response
  • similar to type 1
  • pancreas likely severely damaged
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Euglycemic definition

A

normal blood glucose level

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Gold standard for measuring whole body insulin sensitivity

A

hyperinsulinemia euglycemic clamp

  • measures responsiveness to insulin
  • used in lab, not clinically ($$$)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

hyperinsulinemic euglycemic clamp procedure

A

raise insulin levels to supra-physiological levels via infusion

  • monitor glucose infusion rate (GIR) required to maintain normal/steady blood glucose levels
  • check every 5-10min
19
Q

hyperinsulinemic euglycemic clamp measures

A

High GIR
- >7.5mg/min = very insulin sensitive (athletes)

20
Q

GIR definition

A

glucose infusion rate

  • measured during hyperinsulinemic euglycemic clamp
  • high amounts of insulin infused
  • muscle responds by absorbing resting blood glucose
  • glucose infused at a certain rate to maintain normal glucose levels (euglycemia)
21
Q

Effect of elevated levels of free fatty acids on insulin resistace

A

can induce insulin resistance “in only 4-6hrs”

22
Q

Fatty acid uptake in lean, obese and T2D

- palmate transport rate into muscle

A

HUGE improvement in FA uptake ability in obese and T2D patients (compared to lean and overweight)

23
Q

How does fatty acid uptake improve in obese and T2D patients?

A

FAT/CD36 “redistribution” to plasma membrane

  • huge increase at the plasma membrane
  • NO CHANGE in whole muscle content (homogenate)
24
Q

intergral membrane protein involved in FA transport

A

FAT/CD36

fatty acid translocase / cluster of distribution 36

25
Q

Zucker Rats

A

model for obesity

  • mutation in the “leptin” gene
  • shortened leptin receptor
  • impaired insulin stimulated glucose uptake
  • BUT contraction stimulated glucose uptake normal
26
Q

Effect of obesity/T2D on glucose uptake into muscle

- 2 methods of glucose uptake

A

1) insulin stimulated glucose uptake
- impaired

2) contraction stimulated glucose uptake
- no change*
- ATP turnover to induce AMPK activation can still promote GLUT4 translocation to membrane
* * plasma membrane GLUT4 concentration same levels with exercise

27
Q

IMTG definition

A

Intramuscular triglycerides

- marker of FA storage

28
Q

Athletes paradox

- what does this tell us?

A

General
- declining insulin sensitivity = increase IMTGs
Athletes
- high insulin sensitivity and high IMTGs

Significance

  • IMTGs are an “inert” metabolite unlikely to directly interfere with insulin action
  • does not cause insulin sensitivity
29
Q

IMTG can be used as a marker for what?

A

FA-derived metabolites with negative effects

  • diacylglycerol (DAG)
  • cytosolic long chain fatty acyl CoA (LCFACoA)
  • ceramine
  • *athletes paradox - not bad for them
  • if not used, turned into bad metabolites associated with insulin resistance
30
Q

function of DGAT

A

rate limiting step in TG synthesis
- catalyzes the formation of triglycerides from diacylglycerol (DAG) and acyl-CoA

*remember:
“DAG” and cytosolic long chain fatty “acyl-COA” are bad metabolites that cause insulin resistance

(diglyceride acyltransferase)

31
Q

result of over expressing DGAT

- what is the significance?

A

improve insulin sensitivity
- synthesizes TG

significance

  • TG is the “inert” storage form
  • synthesis of TG is protective
  • other bad metabolites of FA produce cause insulin resistance
32
Q

what is a better predictor for insulin sensitivity/resistance than IMTG

A

LCFACoA (long chain fatty acyl CoA)

  • inverse relationship
  • increase LCFACoA = decrease insulin sensitivity
33
Q

how do fatty acid metabolites suppress insulin signalling cascade?

A

DAG and LCFACoA

  • activate PKC (protein kinase C)
  • phosphorylates serine and theonine residues at IR and IRS-1 (inhibits signalling)

Ceramine
- inhibits akt/PKB and GLUT4 translocase

    • DAG and ceramides do not always coincide with insulin resistance
    • LCFACoA very reactive, suppress insulin signalling and influence fuel supply to mitochondria
34
Q

Key points about LCFACoA

other than insulin signalling

A

1) Inhibits adenine nucleotide translocase (ANT)
- influence fuel supply to mitochondria
- atp from mitochondria to cytosol (out)
- adp from cytosol to mitochondria (in)

2) Promotes reactive oxygen species (ROS) formation
- oxidative stress

  • ** Disease state only
  • ANT “not” inhibited during exercise
  • LCFACoA during chronic state of over eating is in the absence of ADP
  • does not move through system -> builds up
35
Q

What form do we want to store fat

A

IMTG

36
Q

Study: Weight loss in morbidly obese (BMI ~50kg/m2)
- bariatric surgery 142kg -> 80kg in one year

Results?
- insulin sensitivity and lipid storage type

A

Large improvement in insulin sensitivity

  • 25% blood gluc reduction
  • 75% insulin reduction

Change in lipid type

  • LCFACoA reduced
  • mostly palmitoyl CoA and stearyl CoA (saturated FAs)
  • other LCFACoA not as sign
37
Q

Study: weight loss morbidly obese
- 2 year post bariatric surgery

Is fat oxidation improved with weight loss?

A

NO

  • impairment in skeletal muscle fatty acid oxidation persists
  • may contribute to weight re-gain
38
Q

Study: T2D men and women weight loss

  • 16 weeks moderate-intensity exercise
  • caloric restriction

Results?
- insulin stimulated glucose disposal

A

weight loss improved insulin stimulated glucose disposal in those with T2D

  • non oxidative glucose disposal significant increase
  • glycogen formation
39
Q

Study: NO weight loss
- moderate intensity exercise for 8 weeks

Results
- insulin sensitivity and lipids

A

1) Improved insulin sensitivity
- decreased blood glucose and insulin levels

2) Improved CPT1 activity in mitochondria
- allows entry into mitochondria => increased beta oxidation

3) DAGs and ceramides decreased 25-30%
- especially saturated lipid species
- due to FA oxidation? (unknown)

Side notes

  • CPT1 catalyzes acyl-CoA + carnatine => Acyl-Carnatine
  • converted back to acyl-CoA once crossing the membrane before going through beta oxidation
40
Q

Differences in the benefits of weight loss through exercise vs bariatric surgery

A

Both improved insulin sensitivity

Bariatric surgery

  • LCFACoA declined
  • impaired fatty acid oxidation still persisted

Exercise (even with NO weight loss)

  • improved CPT1 activity in mitochondria (increased FA oxidation)
  • DAGs and ceramides decreased 25-30%
41
Q

Conclusions on the problems with lipid metabolism in obesity / diabetes?

A

Not any one thing wrong

  • imbalance between FA uptake and FA oxidation leads to accumulation
  • both transport and oxidation involved in the impairments that occur
  • likely LCFACoA, DAG or ceramides cause problem (not TAG)
  • not fully understood
42
Q

most important component of ‘aerobic’ training to improve “insulin sensitivity”

A

longest duration best

  • regardless of intensity or volume
  • all types benefit
43
Q

resistance training and insulin sensitivity

non obese women - 6 month study

A

improved insulin sensitivity
- when corrected for lean mass => no change

    • improvement due to increase lean muscle mass
  • main tissue for glucose disposal

Nutr 4210 (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions