hormonal regulation of metabolism - lecture

Question 1

stimulators of insulin secretion

Answer 1

glucose - on release and synthesis
AA, esp. arg
FA and ketones
GI hormones - glp-1
parasympathetics

Question 2

inhibitors of insulin secretion

Answer 2

low plasma glucose
low plasma AA
low plasma FA and ketone levels
somatostatin
leptin
catecholamines (via alpha receptors)
sympathetic nervous systems

Question 3

catecholamines in insulin release

Answer 3

normally inhibit
many more alpha receptors than beta so beta is irrelevant
if patient on drugs that inhibit alpha receptors, catecholamines would stimulate insulin release

Question 4

inactivation of insulin

Answer 4

has half-life of about 10 minutes

degraded in liver by an insulin specific protease and glutathione-insulin transhydrogenase

Question 5

glutathione-insulin trashydrogenase

Answer 5

breaks down insulin

Question 6

c-peptide degradation

Answer 6

half-life 30 minutes
not extracted by liver
degraded and excreted by kidney

Question 7

proinsulin degradation

Answer 7

half-life of 20 minutes

degraded mainly in kidney

Question 8

insulin actions in muscle

Answer 8

1: stimulation of glucose uptake into cell (note: exercise and anoxia have comparable action)
2: enhancement of glycogen synthesis
3: stimulation of AA uptake
4: stimulation of protein synthesis
5: inhibition of proteolysis

Question 9

insulin actions in adipose tissue

Answer 9

1: stimulation of glucose uptake into cell
2: activation of lipoprotein lipase
3: inhibition of hormone sensitive lipase (HSL)
4: enhancement of AA uptake and protein synthesis

Question 10

insulin actions in liver

Answer 10

1: increases activities of all rate-limiting glycolytic enzymes
2: decreases activity of all rate-limiting gluconeogenic enzymes
3: increases activity of key lipogenic enzymes and FA synthesis

Question 11

glucagon secretion stimulated by:

Answer 11

low blood glucose
AA (esp arginine)
free FA and glycerol
gut hormones
catecholamines
neural pathways

Question 12

glucagon secretion inhibited by

Answer 12

high blood glucose
insulin
somatostatin

Question 13

rapid actions of glucagon

Answer 13

1: stimulation of glyconeolysis
2: increases cAMP-production and the phos of several protein kinases including the one wihich phos. glycogen synthetase

all actions in liver

Question 14

delayed actions of glucagons

Answer 14

stimulation of gluconeogenesis

Question 15

steps in biosynthesis of catecholamines

Answer 15

1: tyrosine hydroxylase converts L-tyrosine to L-dihydroxyphenyl alanine
2: A. acid decarboxylase converts L-dihydroxyphenyl alanine to L-dopamine
3: dopamine beta-oxidase converts l-dopamine to l-norepinephrine
4: phenylethanolamine n-methyltransferase converts norepi to epi (only in adrenal medulla)

Question 16

inactivation of catecholamines

Answer 16

inactivated very rapidly
can be taken up into storage granules
methylation of phenolic hydroxyl group in position 3 by catechol-O methyl transferase
oxidative deamination by nomamine oxidase
excretion without degradation by kidneys

Question 17

catechol-O methyl transferase

Answer 17

enzyme that inactivates catecholamines by methylating the phenolic hydroxyl group in position 3

Question 18

monamine oxidase

Answer 18

enzyme that inactives catecholamines by oxidative deamination

Question 19

catcholamines in skeletal muscle

Answer 19

1: stimulation of glycogenolysis and lactate production
2: inhibition of glucose uptake and glycogen synthesis

primary effects in muscle (as opposed to glucagon, which has its primary effects in the liver)

Question 20

catecholamines in adipose tissue

Answer 20

stimulation of lipolysis (via activation of hormone-sensitive lipase)

Question 21

catecholamines in liver

Answer 21

comparable to those of glucagon

1: stimulation of glycogenolysis
2: inhibition of glucose oxidation and glycogen synthesis
3: stimulation of gluconeogenesis
4: stimulation of lipolysis

Question 22

anabolic effects of glucocorticoids

Answer 22

1: stimulation of gluconeogenesis and glycogenolysis
2: stimulation of hepatic glycogen synthesis

Question 23

catabolic effects of glucocorticoids

Answer 23

1: inhibition of glucose uptake in adipose and lymphoid tissue, skin, and muscle
2: inhibition of AA uptake in these tissues
3: inhibition of protein and fat synthesis in these tissues
4: stimulation of lipolysis (activation of hormone-sensitive lipase)

Question 24

actions of GH in metabolism

Answer 24

1: stimulation of lipolysis (via activation of hormone-sensitive lipase)
2: inhibition of tyrosine-amino transferase in muscle - protects against catabolizing effects of the glucocorticoids and facilitates shunting of AA into hepatic protein synthesis
3: promotes an early increase in glucose uptake in muscle and adipose tissue (insulin-like action) followed by a decrease in glucose uptake

Question 25

metabolic sequences in untreated type 1 diabetes (for our interest only)

Answer 25

1: insulin lack effects on carbohydrate metabolism result in:
decrease in glucose use
hyperglycemia
glycosurea, osmotic diuresis
water and electrolyte loss
dehydration
hemoconcentration
peripheral circulatory failure
hypotension
low renal and cerebral blood flow
anuria
eventually coma and death
2: effects on fat metabolism result in:
decrease lipogenesis in fat depots
mobilization of depot fat
lipemia
increased ketogenesis in liver
ketonemia
ketonuria with loss of Na
dehydration and hemoconentration
peripheral circulatory failure
hypotension
low renal and cerebral blood flow
anuria
eventually coma and death
3: effects on protein metabolism result in:
increased protein catabolism
aminoacidemia
increased gluconeogenesis
increased urinary nitrogen excretion
loss of K etc. from cells
net loss of body K
cellular dehydration
coma and death