week 1, lecture 3

Question 1

DIAGRAM of the twin cycle hypothesis

Answer 1

xx

Question 2

what happens with insulin resitstance and steatosis

Answer 2

increased gluconeogenesis, increased VLDL export, increased blood glucose and increased insulin pancreatic insulin secretion

Question 4

what receptor does palmitic acid (a FFA) activate?

Answer 4

TLRs –> which exacerbate insulin resistance

Question 5

how does the liver deal with extra FFA

Answer 5

export energy;; VLDL production –> IDL –> LDL –>deliver to other cells

Question 6

what cycle increases blood glucose as a result of liver steatosis

Answer 6

inappropriate GNG

Question 7

which cells of the pancreas are important in adiposity and fibrosis?

Answer 7

acinar cells (and islets)

Question 8

what does the liver deliver to the pancrease

Answer 8

excess triglycerides (via VLDL)

Question 9

what FFA accumulates in pancreatic beta cells

Answer 9

palmitic acid

Question 10

what effect does fatty pancreas have on beta cells

Answer 10

ER stress, ROS, apoptosis of beta cells or de-differentiation (act like alpha cells and secrete glucagon)

Question 11

what is the positive feedback loop seen in the twin cycle

Answer 11

Insulin resistance→increased hepatic steatosis and VLDL output→TG and FFA accumulation in the pancreas→compromised insulin secretion (impaired ability to secrete large, immediate “pulses of insulin)→ hyperglycemia→conversion to fat, increased circulating FFAs

Question 12

what is VLDL mainly made of

Answer 12

TGs

Question 13

what happens if LDL not cleared by hepatocytes

Answer 13

oxidized and becomes a risk factor for atherosclerosis

Question 14

what does adiponectin help with and where is it stores

Answer 14

from subcutaneous fat to regulate glucose levels and breakdown fatty acids.,.. but cant keep up with leptin

leptin: adiponectin ratio increased in T2DM but become resistant to leptin

Question 15

what type of receptors do vascular endothelial cells

Answer 15

insulin receptors
–> vasodilator and constrict –> insulin resistance cause more constriction (decreased NO) and increases hypertension and atherosclerosis

Question 16

insulin resistance impacts on brain

Answer 16

atherosclerosis in vasculature of brain and dementia

Alzheimers from reduced synaptogenesis
and inflammation and glial activation damage neurons

leaky BBB
advanced glycation end products

Question 17

insulin resistance impact on kidneys

Answer 17

sclerosis of glomeruli- damage filtration, kidney infections, arteriolosclerosis, hypertension

Question 18

insulin resistance impact on bone

Answer 18

insulin is anabolic for bones and increases osteoblast activity (build bone) and decrease osteoclast (resorb bone) –> resistance does opposite

overweight stressed bones might be good but in T1D have a lower bone mineral density

Question 19

insulin resistance impact on heart

Answer 19

ER stress, mitochondrial dysfunction, ROS< vascular function, impaired calcium balance effects systole and diastole, angiotensin II, fibrosis, cardiac hypertrophy

Question 20

advanced glycation end products (from hyperglycemia) impact on arteries

Answer 20

pro inflammatory cytokines, ROS, procoagulant, constrict blood vessels via proliferation of vascular smooth muscle, make resistant to proteolysis

–>decrease large artery elasticity, narrow small arteries, deposit atherosclerotic plaques, increase coagulation (blood clots)

activate PKC pathway

Question 21

hyaline arteriolosclerosis (diabetes)

Answer 21

small vessels thicken hyaline walls and narrow lumen

Question 22

diabetic microangiopathy

Answer 22

thicken basement membrane and make capillaries leaky

Question 23

diabetes- neuropathy

Answer 23

loss axons and myelination
loss of pain sensation
postural hypotension, sex dysfunction, bladder emptying incomplete

Question 24

skin condition from T2DM

Answer 24

acathosis nigricans (black leathery skin)

also psoriasis and achordons (skin tags)

Question 25

what are bile acids synthesize from and where?

Answer 25

from cholesterol in hepatocytes

Question 26

what are primary bile acids and what enzymes are used to make them

Answer 26

hydroxylase enzymes to make cholic acid and chenodeoxycholic acid (which then get conjugated with glycine or taurine) to make bile

Question 27

where are bile stored

Answer 27

gallbladder (made in liver)

Question 28

what does bile respond to

Answer 28

CCK and fat/ food in the small intestine

Question 29

what can secondary acids can bile acid turn into in the large intestine and via what

Answer 29

deoxycholic acid and lithocholic acid via microbiota

Question 30

what are the main bacterial enzymes in bile acid processes

Answer 30

Bile salt hydrolases – deconjugation of primary BA’s Hydroxysteroid dehydrogenases – causing oxidation of BA’s Dehydroxylation of unconjugated BA’s

Question 31

bile acid effects

Answer 31

reduce TG biosíntesis and promote clearance reduce hepatic GNG increase brown adipose tissue and BMR promote GLP1 and PYY release (reduce food intake and reduce gastric emptying) promote insulin secretion