18 | Endocrine Pancreas, Metabolism Flashcards
1
Q
fat storage
A
- largest energy reservoir
- stored in adipose tissue as form of triglyceride
- broken down to FFAs (used for B-oxidation) and glycerol (liver converts to glucose)
2
Q
glucose storage
A
- glycogen in the liver
- after a meal can be used by liver or adipose for triglyceride synthesis
3
Q
protein “storage”
A
- protein synthesis from AA’s in all tissues, most active after a meal
- no real storage form, all protein have a purpose
- during fast, protein breakdown in tissues. AA’s used by liver for gluconeogenesis
4
Q
anabolism
A
storage of fuels
5
Q
catabolism
A
mobilization of fuels
6
Q
insulin (general role)
A
regulates anabolism + catabolism
-integrates body fuel metabolism between fed and fasting states
7
Q
fed state
A
anabolic - high insulin
8
Q
carbohydrate digestion
A
increase levels of glucose in blood
9
Q
glucose (stim vs. inh actions)
A
stimulates insulin release
inhibits glucagon release
10
Q
fed state - carbohydrate meal
[brain]
(1)
A
energy needs
11
Q
fed state - carbohydrate meal
[liver]
(5 uses, 3 effects)
A
- energy needs
- converted to glycogen, storage
- converted to triglyceride, exported as lipoproteins
- amino acid synthesis
- nucleic acid synthesis
- inh protein breakdown
- inh glycogen breakdown
- inh glucose synthesis
12
Q
fed state - carbohydrate meal
[muscle]
(1, 2)
A
-increased glucose uptake, energy needs
- stim protein synthesis
- inh protein breakdown
13
Q
fed state - carbohydrate meal
[adipose]
(3, 1)
A
- increased glucose uptake, energy needs
- conversion to triglycerides
- increased TG uptake from circulating lipoproteins, produced by liver
-inh lipolysis
14
Q
protein digestion
A
increased amino acids
- stim insulin production AND
- stim glucagon production (counteracts some insulin effects, prevents hypoglycemia)
15
Q
fed state - protein meal
[brain]
(1)
A
- no use for AA’s alone
- uses glucose made from AA’s in liver
16
Q
fed state - protein meal
[liver]
(3)
A
- AA’s for protein synthesis
- gluconeogenesis (local energy, and glycogen)
- metabolized to TGs, exported as lipoproteins
17
Q
fed state - protein meal
[muscle]
(2)
A
- increased AA uptake, used for protein synthesis
- used for local fuel
18
Q
fed state - protein meal
[adipose]
A
-inc TG uptake from circ lipoproteins produced by liver
19
Q
fat digestion
A
dietary TGs absorbed as FFAs and monoglycerides
- reesterified into TGs, exported from enterocyte in chylomicron, enters lymph
- TGs can be broken down by lipoprotein lipase in adipose capillaries
20
Q
fed state - fat meal
[adipose]
A
FFA’s from TG lipolysis taken up
-used for TG resynthesis (storage)
21
Q
fed state - fat meal
[muscle]
A
takes up FFAs for fuel use
22
Q
post-absorptive state
interprandial) (3
A
decreased insulin
increased glucagon
use of fuel stores
23
Q
post-absorptive state: brain (2)
A
depends on glucose from glycogenolysis and gluconeogenesis in liver
24
Q
post-absorptive state: liver (3)
A
inc glucagon, dec insulin promote
-glycogenolysis
-gluconeogenesis
FFAs from adipose used as fuel
25
post-absorptive state: muscle (3)
- glycogen breakdown
- dec glucose use
- inc FFA uptake for fuel
26
post-absorptive state: adipose (2)
- dec glucose uptake + use
| - inc lipolysis, liberates glycerol and FFAs
27
brief starvation: brain (1)
con't use of glucose from liver gluconeogenesis
28
brief starvation: liver (3)
- glycogen stores depleted
- inc gluconeogenesis, use AA's and lactate
- inc ketone body formation from FFAs, into circ
29
brief starvation: muscle (3)
- glycogen stores depleted
- inc protein breakdown + AA export (for gluconeogenesis)
- dec use of FFAs for fuel, inc use of ketone bodies from liver
30
brief starvation: adipose (1)
-lipolysis + FFA release
31
prolonged starvation: liver (1)
-inc ketogenic enzyme activity, for ketone body formation
32
prolonged starvation: muscle (2)
- after 3-4 days, ketone bodies used as major fuel
| - day 24 switches to FFA for fuel, conserve ketones for brain
33
prolonged starvation: adipose (1)
-lipolysis for FFA release
34
prolonged starvation: brain (1)
-con't to use glucose until day 24, ketone bodies become major fuel
35
exercise (4, 2)
-dec circ glucose
-dec insulin
-dec glucagon
-inc catecholamines
glycogenolysis
gluconeogenesis
36
exercise - muscle (2)
- initial use of local glycogen and TG stores for fuel
| - then use circulation FFAs as fuel (preserve glucose for brain)
37
severe exercise - muscle
-increased dependence of glucose as more fibers are recruit, can preserve as much for brain
38
exercise recovery - muscle (3)
- accelerated replenishing of glycogen stores
- plenty of FFAs for fuel (liberated from exercise), so glucose can be stored not used
- enhanced insulin sensitivity, further promotes glucose uptake + glycogen formation
39
pancreas hormones (4) + their cells
insulin (B cell - 60%)
glucagon (A cell - 20%)
somatostatin (D cell)
pancreatic polypeptide (PP cells)
40
endocrine cells of the pancreas
islets of Langerhans
41
islet structure + blood flow
b-cells located at center
surrounded by other cells
blood flow center out
paracrine regulation of glucagon A-cells by insulin B-cells
42
insulin structure
(in B-cells)
- pre-proinsulin
- ER cleaves to proinsulin (A, B, C chain)
- packaged into secretory vesicles in golgi, in vesicle C peptide (pro) is proteolytically cleaved
- 1:1 ratio, insulin (A+B) : C-peptide
- A+B chains linked by disulfide bridges, required for biological potency
- most C-peptide excreted in urine, can use to measure endogenous insulin levels + B-cell function
43
incretins
intestinal peptide hormones
- greater insulin production following oral glucose vs. IV
- oral glucose stimulates GLIP + GIP (incretins) from endocrine cells of SI
- circulating incretins promote more insulin sec from B-cells for a given level of plasma glucose
44
effects of insulin (4)
fat, carb, protein metabolism
ion flux
growth factor prod
hormone action
45
insulin release stimulators (6)
[reciprocally inhibit glucagon]
glucose (also enhances stimulatory effect of others)
amino acids
fatty acids
catecholamines (B-adrenergic)
neural ACh
intestinal peptide hormones (incretins GLIP + GIP)
46
insulin release inhibitors (4)
catecholamines (a-adrenergic, net inc of catecholamines inhibits insulin sec)
somatostatin
serotonin
prostaglandin E
47
glucose tolerance test
| T1D v. T2D
-capacity to clear glucose from blood w/ 75g oral dose
-measure rise and recovery
-detect insulin resistance or glucose tolerance
T1D: high glucose, little to no insulin
T2D: high glucose, may have high insulin
48
glucose-induced insulin release
1. inc EC gluc, inc IC gluc in B-cell. enters through insulin-insensitive GLUT 2 transporter
2. inc glucose metabolism increases ATP/ADP ratio, closes ATP sensitive membrane K+ channel
3. membrane depolarization (no longer hyperpol)
4. opening of VGCaC, Ca2+ enters cell
5. exocytosis of containing secretory granules
49
insulin receptor functions(on target cells) (2)
1. rec recognizes and binds insulin with high affinity + specificity
2. generate signals that modulate insulin's effector- function
50
insulin receptor structure
- glycoprotein
- 2 EC a subunits, insulin binding site
- 2 TM b subunits, signal transmission
- disulfide bonds a-a, a-b, a-b
- insulin binding activates tyrosine kinase in b subunits
- autophosphorylation of receptor, signaling cascade
51
insulin signaling cascade
- autophosphorylation
- phosphorylation of insulin receptor substrates (IRS-1, -2)
- IRS's bind and activate PI3-K, Grb-SOS and protein tyrosine phosphate (SHPTP2)
- activate downstream enzymes, more specific roles
* many of insulin's effects mediated by phosphorylation and dephosphorylation reactions*
52
insulin receptor activation
- ligand/rec complex rapidly internalized
- insulin lysosomally degraded
- receptor recycled
53
insulin clearance
receptor mediated insulin/rec endocytosis
| impaired ability causes hyperinsulinemia
54
insulin regulation of glucose homoeostasis
controls hepatic glucose production and use of glucose by muscle + adipose
-use determine by rate of glucose transport into cells r
55
glucose transport into cells + role of insulin
muscle + adipose: GLUT-4
- low number of rec on membrane
* glucose transport is rate-limiting for uptake and metabolism*
- insulin increases transport by recruiting GLUT-4 from intracellular pool
56
potassium uptake
- insulin increase uptake of K+ into cells (esp liver + muscle), in absence of glucose movement or pH
- due to insulin increasing activity of Na/K ATPase
- but with low insulin (T1D), can lose K+ in the urine as it leaves cells
- but treatment with insulin can lead to hypokalemia but promoting rapid uptake
57
glucagon stimuli (3, 3)
-falling BG
-inc AA's in plasma (alanine, arginine)
-S-ANS
(inc BG, SS, insulin inh)
58
glucagon in circuation
blood flow from pancreas to liver
- 90% glucagon removed passing liver
- little peripheral effects
59
insulin vs. glucagon (2)
- glucagon has little effect on glucose uptake by muscle
| - shift of anabolism/catabolism in liver are result of changes in insulin/glucagon ration, not absolute amounts
60
glucagon receptor
GPCR linked with AC
| -increase cAMP
61
glucagon in liver
-promotes glycogenolysis
-promotes gluconeogenesis
(leads to increased glucose release)
-increases beta-oxidation of fatty acids
62
type 1 diabetes (general)
"insulin-dependent"
| -viral or immune-mediated destruction of B-cells
63
type 2 diabetes (general)
"non-insulin dependent"
- if insulin deficient, far less than T1. may have normal or high levels.
- insulin resistant
- more common in obese and elderly
64
T1D: lack of insulin effects (2)
uncontrolled fuel catabolism
1. hyperglycemia: high BG, no insulin to reduce it. increased gluconeogenesis.
2. ketoacidosis: high levels of ketone bodies, FFAs from adipose converted to ketones in liver
65
ketoacidosis: starvation
w/ starvation
- gradual
- not associated with hyperglycemia (have insulin)
- only mild acidosis, increased renal NH3 enables H_ clearance
66
diabetic ketoacidosis
- rapid development
- hyperglycemic
- dehyrated due to osmotic diuresis
- high levels of ketone bodies in blood, causing acidosis
- kidney cant increase NH3 fast enough
- w/out insulin muscle can't take up ketone bodies quickly, ends up using FFAs for fuel
- plasma glucose and ketone levels above renal threshold, appear in urine
- Epi/Ne levels increase
67
T2D: effects
- disordered glucose metabolism
| - varying degrees of inability to maintain normal BG, resulting hyperglycemia, and glucose in urine
68
phsyiological risks of T1D + T2D
both at risk for atherosclerosis (T2D more)
| both at risk for eye, kidney, nerve complications (T1D more)
69
3 P's of diabetes
(major clinical manifestations)
polyurea
polydipsia (inc thirst)
-low ECF vol, osmotic diuresis b/c of increase BG
polyphagia (inc appetite)
-"starved" for glucose due to poor uptake into cells
70
sulfonylureas + insulin relase
-stimulate insulin release by blocking ATP-dep K+ channel, facilitate Ca2+ influx, promoting inuslin release
(used in T2D)
71
insulin + T2D
- use exogenous insulin when stimulate of endogenous secretion failed
- could be due to down regulation of receptors, defective receptors, anti-insulin Abs, post-receptor defects
- exogenous insulin important to facilitate glucose use
72
hyperosmolar hyperglycemic nonketonic syndrome
- individual w/ T2D doesn't drink enough fluids
- easer to become dehydrated with high BG
- can lead to stupor as brain becomes dehydrated
73
3 -pathy's of diabetes
retinopathy
-inc risk for glaucoma and cataracts
neuropathy
-poor circulation + wound healing. decreased sensation - minor injuries unnoticed, can lead to infection and amputation. dec circ can also lead to arterial disease.
nephropathy
-kidney failure, degradation of microvasculature
74
hypoglycemia symptoms
- adrenergic: activation of S-ANS leads to sweating, weakness, palpitation, tremor, hunger, nervousness
- neuroglycopenic: CNS symptoms such as headache, confusion, visual disturbances, motor weakness, personality changes
