Endocrine control of metabolism Flashcards
True or false: The brain can use multiple sugar sources to make ATP
False
- The brain can only use glucose to make ATP
Which 3 organs use ATP directly from glucose after a meal?
- Brain
- Kidneys
- Muscle
What 3 organs/tissues store glucose after a meal?
- Liver (glycogen)
- Adipose tissue (glucose is converted into fat, which is more energy dense)
- Muscle (glycogen)
Glycogenolysis
The breakdown of glycogen to produce glucose 6-phosphate, which can become glucose
Glycogen synthesis/glycogenesis
The production of glycogen from glucose
Glycolysis
Production of pyruvate from glucose
Gluconeogenesis
Production of glucose from non-glucose sources (e.g. fats, amino acids, pyruvate, etc.)
After glycolysis, pyruvate can be converted into which three molecules?
- Amino acids
- Lactate
- Acetyl CoA
Where are the endocrine cells of the pancreas contained?
In the pancreatic islets or islets of Langerhans
α cells (islet of Langerhans cells) produce…
Glucagon
β cells (islet of Langerhans cells) produce…
Insulin
δ cells (islets of Langerhans cells) produce…
Gastrin and Somatostatin (which is produced in the hypothalamus as well, remember that it blocks growth hormone)
Which cells make up the majority of the islet?
β cells
Which cells are the most scarce on islets?
δ cells
Main hypoglycemic hormone
Insulin
Main hyperglycemic hormone
Glucagon
Insulin functions (4)
Reduces blood glucose levels by…
1. Increasing glucose transport into insulin sensitive cells
2. Enhancing cellular utilization and storage of glucose
3. Enhancing utilization of amino acids
4. Promoting fat synthesis
Glucagon function
Acts on liver cells to increase formation of glucose and results in increased circulating glucose levels
- Breaks down glycogen in the liver
- Stimulates gluconeogenesis
How many amino acids in insulin?
51
How many amino acids in glucagon?
29
Increased glucose directly (stimulates/inhibits) beta cells in the pancreas
Stimulates
Increased amino acids directly (stimulates/inhibits) beta cells in the pancreas
Stimulate
Increased GI hormones directly (stimulates/inhibits) beta cells in the pancreas
Stimulate
GI hormones (3)
- Gastrin
- Secretin
- Cholecytokinin
Sympathetic activity (stimulates/inhibits) beta cells in the pancreas
Inhibits
Neurotransmitter and hormone in human sympathetic nervous system
Neurotransmitter: Noradrenaline
Hormone: Adrenaline
Hormone in human parasympathetic nervous system
acetylcholine
Glucose activation of beta cells is via what receptor?
Calcium-dependent membrane receptor, known as a glucose-sensing receptor, which leads to the direct activation of insulin
Decreased blood glucose levels (stimulate/inhibit) beta cells through…
Inhibit beta cells through stimulation of catecholamines. The catecholamines then bind to the alpha adrenergic receptors on pancreatic beta cells to inhibit insulin production and act on pancreatic alpha cells to stimulate glucagon production
Catecholamines bind __ receptors on __ cells to (stimulate/inhibit) insulin production
Catecholamines bind alpha receptors on beta cells to inhibit insulin production
Catecholamines bind __ receptors on __ cells to (inhibit/stimulate) glucagon production
Catecholamines bind beta receptors on alpha cells to stimulate glucagon production
Somatostatin produced in the pancreas by delta cells (stimulates/inhibits) pancreatic beta cells
Inhibits
Describe the structure of insulin
Consists of 2 chains A and B connected by S-S bonds, called a C-peptide
Precursor for insulin
A single chain larger peptide (proinsulin, 81 amino acids)
- Part of the molecule C-peptide is removed during cellular processing
After eating a meal, there is an (immediate/prolonged) rise in insulin levels
Immediate
Insulin increases the transport of glucose in what three cells?
Muscle, heart and adipose cells
True or false: insulin can cross the blood-brain barrier
False, it’s too large
- Which is why insulin doesn’t increase glucose transport in renal tubules, RBC, intestinal mucosa, liver and brain.
Insulin increases the glucose transport via…
Insulin-dependent glucose transporters (e.g. GLUT 4)
Insulin effect of amino acids
Insulin increases the transport of amino acids (because insulin stimulates protein production)
Insulin effect on fatty acids
Increases transport of fatty acids (because insulin stimulates lipogenesis)
Insulin effect on glucose oxidation in adipose tissue
Insulin increases glucose oxidation in adipose tissue (because if you want to build proteins, you need ATP)
Insulin effect on glucose storage, primarily in muscle
Insulin increases glycogenesis (primarily in muscle)
How does insulin increase glycogenesis in the muscle?
Insulin increases hepatic glucokinase activity which catalyzes the phosphorylation of glucose into glucose 6-phosphate. Glucose 6-phosphate is then converted into glycogen, as insulin also stimulates glycogen synthesis
Insulin (increases/decreases) the activity of lipoprotein lipase, which (increases/decreases) fat synthesis
Insulin increases the activity of lipoprotein lipase, which increases fat synthesis
Insulin (increases/decreases) fat oxidation, which (increases/decreases) lipolysis
Insulin decreases fat oxidation, which decreases lipolysis
Insulin (increases/decreases) amino acid transport into ____ cells and protein synthesis
Insulin increases amino acid transport into fat cells and protein synthesis
Insulin (increases/decreases) protein catabolism
Decreases
Type I diabetes mellitus is also known as…
Insulin-dependent diabetes
Type II diabetes mellitus is also known as…
Non-insulin-dependent diabetes
Describe Type I diabetes mellitus
An autoimmune disorder in which the immune system destroys the beta cells of the pancreas
Type I diabetes mellitus treatment
Need to take recombinant insulin injections
Decribe Type II diabetes mellitus
Is characterized either by a deficiency of insulin or, more commonly, by reduced responsiveness of target cells due to some change in insulin receptors
- Linked to obesity
- Causes neuropathy (degeneration of nerves)
What 7 hormones oppose insulin action?
- Glucagon
- Cortisol
- Adrenaline
- GH
- T3, T4
- Prolactin (pregnancy)
- Estrogens
Glucagon has a very (slow/rapid) effect on increasing blood glucose
Rapid
Epinephrine has a more (rapid/prolonged) effect than glucagon on increasing blood glucose levels
Prolonged
Glucagon + epinephrine combined (which is normal) effect on blood glucose
Increases blood glucose
Glucagon + epinephrine + cortisol effect on blood glucose levels
Increases rapidly and for a long time
- This is what happens when we have a chronic stress response
The synergistic effects of cortisol, epinephrine and glucagon is (lower/higher) than their individual hormone effects
Higher
Low blood glucose levels DIRECTLY (activate/inhibit) alpha cells by binding to its (alpha/beta) receptors
Activate, beta
Low blood glucose levels INDIRECTLY (activate/inhibit) alpha cells by…
Activate
- producing catecholamines that bind to the beta receptors of alpha cells
Describe how low blood glucose directly triggers glucagon secretion by activating alpha cells (4 steps)
- Hypoglycemia causes low intracellular glucose concentration, leading to a reduction in glycolysis-generated ATP
- Reduction in ATP-sensitive potassium (K+) channel activity
- Increase in intracellular K+ causes depolarization of the cell membrane and activation of voltage-dependent Ca2+ channels
- Increased influx of Ca2+ triggers the secretion of glucagon through exocytosis
What 3 things does glucagon stimulate?
- Increase glycogenolysis
- Increase gluconeogenesis
- Increase lipolysis
Describe how glucagon increases glycogenolysis
- Binds to GPCR coupled to Gs
- Gs activates PKA
- PKA phosphorylates both glucose 6-phosphatase and glycogen phosphorylase
- Glycogen phosphorylase converts glycogen into glucose 1-phosphate.
- Glucose 1-phosphate quickly converts into glucose
Most direct/fastest effect of glucagon
Increasing glycogenolysis
Glycogenolysis occurs mostly in… (2)
The liver and skeletal muscle
How does glucagon affect proteins?
Glucagon increases amino acid mobilization from protein
- Prolonged starvation breaks down muscle, because brain needs glucose (brain>rest of body)
How does glucagon affect amino acids?
Results in deamination of amino acids in the liver and its conversion to carbohydrate (gluconeogenesis)
What is gluconeogenesis in general?
Synthesis of glucose from non-carbohydrate sources (protein and fatty acids)
Where does glucagon increase lipolysis?
Glucagon increases lipolysis primarily in the fat cells and liver, which increases fatty acids.
- Fatty acids can then be converted into glycogen and then released as glucagon.
Adrenal glands are on top of…
Renal tissue (kidneys)
Hormones secreted by adrenal medulla (3)
What class are these hormones?
Catecholamines
1. Epinephrine (E) or adrenaline
2. Norepinephrine (NE) or noradrenaline
3. Dopamine (DA)
2 classes of hormones secreted by adrenal cortex
- Glucocorticoids (important in carbohydrate metabolism)
- Mineralocorticoids
What organ other than gonads secrete steroids?
Adrenal cortex
Adrenal glands are composed of an inner ______ and outer ______
Adrenal glands are composed of an inner medulla and outer cortex
The ______ tissue in the adrenal medulla secretes catecholamine hormones and the _____ secretes steroids
The chromaffin tissue in the adrenal medulla secretes catecholamine hormones and the cortex secretes steroids
What is a potential Parkinson’s treatment using chromaffin tissue?
Put chromaffin tissue in the brain to produce more dopamine.
Zonas in cortex from most superficial layer to deepest
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
Zona glomerulosa produces…
(2)
corticosterone, aldosterone (mineralocorticoid)
Zona Fasciculata produces…
(1)
Glucocorticoids (cortisol)
Zona reticularis produces…
(1)
Gonadocorticoids (androgens)
The medullary cells contain the enzyme ______ which synthesizes epinephrine from norepinephrine
Phenylethanolamine-N-methyltransferase (PNMT)
Synthesis of catecholamines steps (5)
- Phenylalanine converts into Tyrosine from Phenylalanine hydroxylase
- Tyrosine converts into dihydroxyphenylalanine (DOPA) from tyrosine hydroxylase (rate limiting enzyme)
- DOPA converts into dopamine from dopa decarboxylase
- Dopamine converts into norepinephrine from dopamine β-hydroxylase
- Norepinephrine converts into epinephrine from phenylethanolamine-N-methyltransferase (PNMT)
Rate-limiting enzyme in synthesis of catecholamines pathway
Tyrosine hydroxylase
- When downregulated, rest of pathway does not occur
True or false: phenylethanolamine-N-methyltransferase (PNMT) enzyme is abundant in the brain
False
- PNMT is abundant in the adrenal medulla.
- norepinephrine is produced in the brain instead (not converted into epinephrine)
What molecules act as negative feedback on tyrosine hydroxylase in the synthesis of catecholamines?
Dopamine and norepinephrine.
Norepinephrine acts as a _____ in humans, while epinephrine acts as a _____.
Norepinephrine acts as a neurotransmitter in humans, while epinephrine acts as a circulating hormone (systemic hormone).
What are the types of membrane-associated adrenergic receptors?
Alpha and beta
What are the subgroups of the alpha and beta receptors on adrenergic receptors?
α1, α2
β1, β2
True or false: All adrenergic receptors are sensitive to both epinephrine and norepinephrine, but there are differences in their potencies
True
The adrenergic receptors are what type of receptors?
GPCRs that are coupled to both Gs and Gq
In general, epinephrine prepares the body for…
Physical response to emergency situations resulting from fear, emotional stress, hypoxia, cold, hypoglycemia, etc.
The primary adrenal medulla hormine in mammals is….
Epinephrine
(epinephrine/norepinephrine) is is more able to elicit a generalized response than (epinephrine/norepinephrine)
Epinephrine, norepinephrine
Epinephrine effect on circulating glucose level
Increase circulating glucose level
- acts on glycogen to release glucose into blood for uptake by cells
Epinephrine effect on cardiac output
Increases cardiac output (increases oxygen supply due to heart rate)
Epinephrine effect on blood supply
Elicits redistribution of the blood supply
- Blood flow to the part of body not involved in muscular activity such as skin and gut are restricted.
- Blood supply to skeletal muscle increased
Epinephrine effect on pulmonary ventilation
Stimulates pulmonary ventilation by dilation.
- Increased breathing rate = increased oxygen supply
- Reason why we use EpiPen during anaphylactic shock -> prevents suffocation
Epinephrine effect on sweat glands
Epinephrine also acts on sweat glands and increases sweating -> why you sweat when you’re stressed -> has nothing to do with thermoregulation
Adrenaline causes (hypoglycemia/hyperglycemia)
Hyperglycemia
What 4 things does adrenaline stimulate?
- Hepatic glycogenolysis (immediate response)
- Hepatic gluconeogenesis by mobilizing fat and amino acids for gluconeogenesis (more prolonged action)
- Stimulation of glucagon release (beta receptor)
- Stimulation of ACTH release
What does adrenaline inhibit
Insulin release (alpha receptor on beta cells)
(norepinephrine/epinephrine) has increased potency for alpha receptors
Norepinephrine
(norepinephrine/epinephrine) has increased potency for beta receptors
Epinephrine
Norepinephrine (stimulates/inhibits) gluconeogenesis
Stimulates
Norepinephrine (dilates/constricts) pupils
Dilates
Norepinephrine (stimulates/inhibits) sweating
STimulates
Norepinephrine (stimulates/inhibits) insulin secretion
Inhibits
Norepinephrine (stimulates/inhibits) growth hormone secretion
Stimulates
Norepinephrine (dilates/constricts) arteries in the renal and cutaneous tissue
Constricts
Norepinephrine (stimulates/inhibits) muscle contraction in the gastrointestinal and urinary tissue
Stimulates
(norepinephrine/epinephrine) has increased potency for beta adrenergic receptors
Epinephrine
Epinephrine (stimulates/inhibits) glycogenolysis
Stimulates
Epinephrine (stimulates/inhibits) lipolysis
Stimulates
Epinephrine (stimulates/inhibits) renin secretion and uses (β1, β2) receptors
Epinephrine stimulates renin secretion and uses β2 receptors
Epinephrine (stimulates/inhibits) arteriolar dilation
Stimulates
Epinephrine (increases/decreases) cardiac contractility and uses (β1, β2) receptors
Increases, β1
Epinephrine (increases/decreases) heart rate and uses (β1, β2) receptors
Increases, β1
Epinephrine (stimulates/inhibits) muscle relaxation in the GI, bronchial and urinary tracts and uses (β1, β2) receptors
Stimulates, β2
Epinephrine (stimulates/inhibits) glucagon secretion
Stimulates
Epinephrine (stimulates/inhibits) thyroid hormone secretion
Stimulates
What type of hormones does the adrenal cortex secrete?
Corticosteroids
CRH (corticotropin releasing hormone) (stimulates/inhibits) the hypothalamo-hypophyseal-adrenal axis
Stimulates
Glucocorticoids (stimulate/inhibit) the hypothalamo-hypophyseal-adrenal axis
Inhibit
- through negative feedback
Catecholamines and opioids (stimulate/inhibit) the hypothalamo-hypophyseal-adrenal axis
Both stimulate and inhibit, but opioids generally inhibit
Stress (stimulates/inhibits) the hypothalamo-hypophyseal-adrenal axis
Stimulates
- any type of stress, like chemical stress or physical stress
- When the body perceives stress, the hypothalamus releases corticotropin-releasing hormone (CRH), which then stimulates the anterior pituitary gland to secrete adrenocorticotropic hormone (ACTH). ACTH acts on the adrenal cortex, prompting it to release cortisol, the body’s main stress hormone.
Aldosterone general function
In kidney, regulates water and salt uptake
Cortisol main function
Increase metabolic fuel: circulating glucose (rather than keeping glucose stored), amino acids and fatty acids
-opposes insulin action
What does the metabolic activity of glucocorticoids (e.g. cortisol) result in in terms of carbohydrates?
Results in availability of energy in a form of readily usable carbohydrate
What do glucocorticoids stimulate in terms of proteins and fats?
(Main effect of cortisol?)
The breakdown of proteins and fats and their conversion into carbohydrates (gluconeogenesis).
Main site of metabolism?
Hepatocytes
- Also more “leaky” (have a higher permeability to solutes than other cells)
Cortisol stimulates what in the liver?
The conversion of glucose to glycogen
- Not the main effect
Glucocorticoids inhibit what in certain cells (including what cell specifically?)
Uptake of glucose and amino acids by certain cells including adipose tissue
Glucocorticoid effect in skeletal muscle and adipose tissue is (anabolic/catabolic)
Catabolic
Glucocorticoid effects in skeletal muscle and adipose tissue
Increase proteolysis of muscle proteins and lipolysis of fat and increase fatty acids and amino acids for gluconeogenesis in the liver.
ACTH
a) belongs to glycoprotein family of hormones
b) belongs to the same family as prolactin hormone
c) is a POMC derived peptide
d) belongs to the same family as oxytocin
e) none of these answers
C
__ (P, polypeptide; S, steroid) hormones of the adrenal cortex, ovaries, and tested mainly act upon (M, cell membrane; I, intracellular) receptor proteins to activate __ (G, specific genes; A, adenylylcyclase)
S, I, G
Glucagon is coupled to what G protein? What does this result in?
Glucagon is coupled to Gs, with increases the amount of PKA in the cell. PKA phosphorylates/activates glycogen phosphorylase and glucose 6-phosphatase
Give 4 examples for the effect of norepinephrine binding the (alpha/beta) receptors with greater potency
Alpha
1. Dilation of pupils
2. Sweating
3. Decreased insulin secretion
4. Increased GH secretion
Give 4 examples for the effect of epinephrine binding the (alpha/beta) receptors with greater potency
Beta
1. Increased lipolysis
2. Increased cardiac contractility (beta1)
3. Increased heart rate (b1)
4. Renin secretion (Beta2)
