fed and fasting Flashcards
1
Q
main hormones of metabolism
A
- insulin: hypoglycaemic hormone
- glucagon: hyperglycaemic
- adrenaline: in adrenal medulla
2
Q
other insulin counter regulatory hormones
A
adrenaline - adrenal medulla
cortisol - adrenal cortex
growth hormone. - anterior pituitary
3
Q
islets of langerhans
3 types of cells
A
2% pancreatic mass adult: 1million islets B cells (60-70%) secrete insulin a cells (30-40%) secrete glucagon delta cells secrete somatostatin
4
Q
insulin secretion stimulated by
A
- increase blood glucose
- increase amino acid conc
- gut hormones: secretin and other GI hormones
- glucagon: fine tune glucose homeostasis
5
Q
insulin inhibited by..
A
adrenaline
6
Q
describe steps to insulin secretion
A
- glucose
- glycolysis - production of ATP (metabolise a.acid)
- block K channels
- Ca channels open
- Ca increases in cell
- vesicle containing insulin secreted
7
Q
what is secretion of glucagon stimulated bu
A
- low blood glucose
- high conc of amino acid in blood (prevent hypoglycaemia after protein meal)
- adrenaline: block insulin secretion.
8
Q
metabolic effects of insulin
A
- promote fuel storage after meal
- promote growth
- stimulate glycogen synthesis and storage
- stim fatty acid synth and storage from CHO when intake exceeds glycogen storing capacity
- stim amino acid uptake and protein synthesis (liver and muscle cells)
9
Q
role of insulin in terms of receptors on diff tissues
A
- -promote GLUT4 transporters in muscle and adipose tissue
- brain, liver, erythrocyte and pancreas have GLUT - not insulin dependent
- high insulin conc = down-regulation of its receptors
- effects vary in time: Glc transporters and activation is rapid, synthesis of enzymes is slow
10
Q
what does glucagon do during fasting
A
- mobilise fuel and maintain blood glc during fasting
- activate glycogenolysis and gluconeogenesis in liver
- activate a.acid uptake by liver for gluconeogenesis
- FA release from adipose tissue
- FA oxidation and ketone boy formation in liver
11
Q
what does adrenaline do during stress
A
mobilise fuel during stress:
- stim glycogenolysis (muscle and liver)
- stim FA release from adipose tissue
12
Q
what does cortisol do
A
provide long term needs:
- stim aa mobilisation from muscle
- stim gluconeogenesis
- FA release fro adipose tissue
13
Q
fed (absorptive) state:
when is it
main things that happen during this time in terms of glucose, aacid, TAG
A
2-4 hrs after meal
- increase blood glucose,, amino acids and TAG as chylomicrons
- synth/store glycogen, TAG and protein
- liver receives nutrients before other tissues - hepatic portal vein
14
Q
when does the liver do gluconeogen and explain why
A
- liver does gluconeogenesis always except in fed state (high insulin/glucagon ratio)
- glycogen synthase active, phosphorylase inhibited
- high Km for glucose = no competition with brain when glc low
15
Q
how is glycolysis activated in the liver
A
fed state: activate glucokinase.
also activated through PFK and pyruvate kinase
16
Q
describe liver fat metabolism
A
- FA and TAG synthesis activated
- acetyl CoA carboxylase activated
- malonyl CoA inhibits carnitine transferase
- new FA becomes esterified to TAG - does not enter mitochondrion for oxidation
17
Q
brain and erythrocyte
A
- rely on glc: FA can’t cross blood-brain barrier and erythrocyte has no mitochondria
- glc transport is independent of insulin (GLUT1)
- use of glc at high and low conc
18
Q
muscle
A
- GLUT4 transporters increase in number
- activate glycogen synthesise and inhibit phosphorylase in liver
- activate amino acid uptake and increase protein synthesis
19
Q
adipose tissue
A
- lipoprotein lipase activated by insulin. Allows entry of FA for esterification and storage of TAG
- GLUT4
- glc needed to produce glycerol phosphate and esterification of TAG
- hormone sensitive lipase: inhibited so TAG isn’t degraded
20
Q
fasting state (post-absorptive)
A
- blood glc peak an hour after eating
- normal blood 2 hrs after meal
- blood glc removed for oxidation or storage
- glucagon conc rises, insulin drops
21
Q
fasting: liver and adipose
A
- liver maintains blood glc conc at 4mM
- adipose provides most energy as TAGs
- hormone sensitive lipase activated by glucagon and adrenaline
- FA transported to liver boun to albumin
22
Q
glucose production by liver (fasting)
A
- glycogen
- gluconeogenesis follows from lactate (erythrocytes and muscle, glycerol (adipose), amino acids (muscle)
- after 24hrs fasting, all blood glc comes from gluconeogenesis
23
Q
why can’t FA be used to make glucose (fasting) in liver
A
- FA is nto a gluconeogenic precursor
- pyruvate dehydrgenase reaction (pyruvate->acetyl CoA) is irreversible
- PDH activated by insulin, inhibited by glucagon
- ensure gluconeogenic substrates channeled into glc production, not A.CoA. (we get enough CoA from FA)
24
Q
how is conversion of pyruvate to acetyl CoA inhibited
A
insulin??
acetyl CoA inhibits pyruvate hydrogenase.
25
what are 2 ketone bodies released into the bloodstream
acetoacetate and B-hydroxybutyrate
26
why are ketone bodies used
too many acetyl CoA made by oxidation of FA to enter the TCA cycle.
Most tissues oxidise a mix of FA and KB
erythrocytes use glucose, brain uses glc and KB
27
how much protein can be used in prolonged starvation before fatal consequences
a third of body protein
28
explain the difference in urea excretion in fed and fasting state
large amount of urea produced 12hrs after food. decreases 3 days and 5-6weeks after.
Lots of muscle breakdown at the start.
decreases as the brain is using ketone bodies, so less muscle breakdown
29
what happens as starvation continues?
- muscles use FA rather than KB
- [FA] plateau, KB rise
- brain can use more KB, less glucose
- need for gluconeogenesis is reduced, muscle protein breakdown decreases
- less urea production
30
what do ketone bodies do?
-act on pancreatic B cells - stimulate insulin release
-limits muscle proteolysis
-limits adipose tissue lipolysis
preserves muscle tissue.
31
what events lead up to death?
fuel exhaustion, loss of function due to loss of protein, impairment of immune system
32
what is an important determinant of survival?
amount of adipose tissue
33
how long can one starve for before death?
40days (perhaps longer if young and fit)
| death from starvation often due to infection
34
other names for type 1 and 2 diabetes
1: insulin dependent diabetes mellitus IDDM
2: non-insulin dependent diabetes mellitus
10-20% diabetics are IDD
35
diabetes
2-3% pop affected
90% endocrine disorders
cause blindness, amputations, premature deaths
-5-10% total health care budget
36
diabetes type 1: cause, symptoms and treatment
- autoimmune destruction of B cells
- early onset
- polyuria, polydipsia, polyphagia (excessive eating), fatigue, weight loss, muscle wasting, weakness
- hyperglycaemia, ketoacidosis
- insulin treatment
37
diabetes type 2: cause, symptoms and treatment
- later onset
- insulin resistance
- diet and lifestyle
- hyperglycaemia but no ketoacidosis
- diet and oral hypoglycaemic agents
38
what are the metabolic patterns during starvation in a diabetic
similar response to starvation but more exaggerated:
- low insulin (type 1-absent)
- unopposed glucagon acts
- KB produced in starvation = insulin release
- limit muscle protein breakdown, release of FA from adipocytes and uncontrolled production of KB
- this important mechanism does NOT operate in diabetes
39
Chronic complications of diabetes mellitus
Microangiopathy: changes in walls of small blood vessels seen as thickening of basement membrane
• Retinopathy: blindness is 25 x more common in the diabetic patient
• Nephropathy: renal failure 17 x more common
• Neuropathy: postural hypotension, impotence, foot ulcers
40
treatment of diabetes 1
1: exogenous insulin by injection. Important to balance dosage with amount of food to avoid hypoglycaemic incidents, the most common complication of insulin therapy
41
treatment of diabetes 2
2:weight reduction, dietary modification, oral hypoglycaemic agents
• biguanides increase the number of glut4
• sulphonylureas act on the β cell to improve insulin secretion
42
describe metabolic syndrome
```
WHO:
Metabolic syndrome
• High fasting glc/insulin resistance/diabetes type 2/impaired GT
• Plus2of:
• Hypertension
• Dyslipidaemia (high TAG/low HDL
• Central obesity
• microalbuminuria
```
43
metabolism in diabetes
- excessive protein breakdown
- excessive gluconeogenesis
- fat breakdown, leading to KB production
- unopposed
