2. Hormone Activity
The Role of Hormone Receptors
Although a given hormone travels throughout the body in the blood, it affects only
specific target cells.
Hormones, like neuro-transmitters, influence their target cells by chemically
binding to specific protein receptors.
Only the target cells for a given hormone have receptors that bind and recognize
that hormone.
For example, thyroid-stimulating hormone (TSH) binds to receptors on cells of the
thyroid gland, but it does not bind to cells of the ovaries because ovarian cells do
not have TSH receptors.
Receptors, like other cellular proteins, are constantly being synthesized and broken
down.
Generally, a target cell has 2000 to 100,000 receptors for a particular hormone
3. Circulating Hormones
Most endocrine hormones are circulating hormones.
They pass from the secretory cells that make them into
interstitial fluid and then into the blood.
4. Local hormones
They act locally on neighboring cells or on the same cell that
secreted them without first entering the bloodstream.
Local hormones that act on neighboring cells are called paracrines.
And those that act on the same cell that secreted them are called
autocrines.
5. An example of a local hormone is the gas nitric oxide (NO).
◦ It is released by endothelial cells lining blood vessels.
◦ NO cause relaxation of nearby smooth muscle fibers in blood
vessels, which in turn causes vasodilation (increase in blood
vessel diameter).
Local hormones usually are inactivated quickly.
Circulating hormones may linger in the blood and exert their
effects for a few minutes or occasionally for a few hours.
In time, circulating hormones are inactivated by the liver and
excreted by the kidneys.
6. Chemical Classes of Hormones
Chemically, hormones can be divided into two broad
classes:
◦ Those that are soluble in lipids
◦ Those that are soluble in water
This chemical classification is also useful functionally
because the two classes exert their effects differently.
7. Lipid-Soluble Hormones
Steroid hormones
◦ They are derived from cholesterol.
◦ Each steroid hormone is unique due to the presence of different
chemical groups attached at various sites on the four rings at the
core of its structure.
◦ These small differences allow for a large diversity of functions.
Two thyroid hormones (T3 and T4)
◦ They are synthesized by attaching iodine to the amino acid
tyrosine.
◦ The presence of two benzene rings within a T3 or T4 molecule
makes these molecules very lipid-soluble.
The gas nitric oxide (NO)
◦ It is both a hormone and a neurotransmitter.
◦ Its synthesis is catalyzed by the enzyme nitric oxide synthase.
8. Water-Soluble Hormones
Amine hormones
◦ They are synthesized by decarboxylating and otherwise
modifying certain amino acids.
◦ They are called amines because they retain an amino group (-
NH3
+).
◦ The catecholamines— epinephrine, norepinephrine, and
dopamine—are synthesized by modifying the amino acid
tyrosine.
◦ Histamine is synthesized from the amino acid histidine by mast
cells and platelets.
◦ Serotonin and melatonin are derived from tryptophan.
9. Peptide hormones and protein hormones
◦ They are amino acid polymers.
◦ The smaller peptide hormones consist of chains of 3 to 49 amino
acids.
◦ Examples of peptide hormones are antidiuretic hormone and
oxytocin.
◦ The larger protein hormones include 50 to 200 amino acids.
◦ Examples of protein hormones include human growth hormone and
insulin.
◦ Several of the protein hormones, such as thyroid-stimulating
hormone, have attached carbohydrate groups and thus are
glycoprotein hormones.
Eicosanoid hormones
◦ They are derived from arachidonic acid, a 20-carbon fatty acid.
◦ The two major types of eicosanoids are prostaglandins and
leukotrienes.
◦ The eicosanoids are important local hormones, and they may act as
circulating hormones as well.
10. CHEMICAL
CLASS
HORMONES SITE OF SECRETION
LIPID-SOLUBLE
Steroid hormones
Aldosterone, cortisol, androgens
Calcitriol
Testosterone
Estrogens, progesterone
Adrenal cortex
Kidneys
Testes
Ovaries
Thyroid hormones T3 (triiodothyronine), T4 (thyroxine) Thyroid gland (follicular cells)
Gas Nitric oxide (NO)
Endothelial cells lining blood
vessels
11. WATER-SOLUBLE
Amines
Epinephrine,norepinephrine (catecholamines)
Melatonin
Histamine
Serotonin
Adrenal medulla
Pineal gland
Mast cells in connective tissues
Platelets in blood
Peptides
and proteins
All hypothalamic releasing and inhibiting
hormones.
Oxytocin, antidiuretic hormone.
Human growth hormone, thyroid-stimulating
hormone, adrenocorticotropic hormone,
follicle-stimulating hormone, luteinizing
hormone, prolactin, melanocyte-stimulating
hormone.
Insulin, glucagon, somatostatin, pancreatic
polypeptide.
Parathyroid hormone.
Calcitonin.
Gastrin, secretin, cholecystokinin, GIP
(glucose-dependent insulinotropic peptide).
Erythropoietin.
Leptin.
Hypothalamus
Posterior pituitary
Anterior pituitary
Pancreas
Parathyroid glands
Thyroidgland (parafollicularcells)
Stomach and small intestine
(enteroendocrine cells)
Kidneys
Adipose tissue
Eicosanoids Prostaglandins, leukotrienes All cells except red blood cells
12. Hormone Transport in the Blood
Most water-soluble hormone molecules circulate in the watery
blood plasma in a “free form” not attached to other molecules.
But most lipid-soluble hormone molecules are bound to transport
proteins.
The transport proteins are synthesized by cells in the liver.
In general, 0.1–10% of the molecules of a lipid-soluble hormone are
not bound to a transport protein.
This free fraction diffuses out of capillaries, binds to receptors, and
triggers responses.
As free hormone molecules leave the blood and bind to their
receptors, transport proteins release new ones to replenish the free
fraction.
13. Mechanisms of Hormone Action
The response to a hormone depends on both the hormone and the target cell.
Various target cells respond differently to the same hormone.
Insulin, for example, stimulates synthesis of glycogen in liver cells and synthesis
of triglycerides in adipose cells.
The cellular response to a hormone
◦ synthesis of new molecules
◦ changing the permeability of the plasma membrane
◦ stimulating transport of a substance into or out of the target cells
◦ altering the rate of specific metabolic reactions
◦ causing contraction of smooth muscle or cardiac muscle
A hormone must first “announce its arrival” to a target cell by binding to its
receptors.
The receptors for lipid-soluble hormones are located inside target cells.
The receptors for water-soluble hormones are part of the plasma membrane of
target cells.
14. Action of Lipid-Soluble Hormones
The lipid-soluble hormones, including steroid hormones and thyroid
hormones, bind to receptors within target cells.
Their mechanism of action is as follows:
1. A free lipid-soluble hormone molecule diffuses from the blood, through
interstitial fluid, and through the lipid bilayer of the plasma membrane
into a cell.
2. If the cell is a target cell, the hormone binds to and activates receptors
located within the cytosol or nucleus. The activated receptor–hormone
complex then alters gene expression: It turns specific genes of the
nuclear DNA on or off.
3. As the DNA is transcribed, new messenger RNA (mRNA) forms, leaves
the nucleus, and enters the cytosol. There, it directs synthesis of a new
protein, often an enzyme, on the ribosomes.
4. The new proteins alter the cell’s activity and cause the responses typical
of that hormone.
15.
16.
17. Action of Water-Soluble Hormones
They cannot diffuse through the lipid bilayer of the plasma membrane
and bind to receptors inside target cells.
Instead, water-soluble hormones bind to receptors that protrude from
the target-cell surface.
The receptors are integral transmembrane proteins in the plasma
membrane.
When a water-soluble hormone binds to its receptor at the outer surface
of the plasma membrane, it acts as the first messenger.
The first messenger (the hormone) then causes production of a second
messenger inside the cell, where specific hormone-stimulated
responses take place.
One common second messenger is cyclic AMP (cAMP).
Neurotransmitters, neuropeptides, and several sensory transduction
mechanisms also act via second-messenger systems.
18.
19. The action of a typical water-soluble hormone occurs as follows:
1. A water-soluble hormone (the first messenger) diffuses from the
blood through interstitial fluid and then binds to its receptor at the
exterior surface of a target cell’s plasma membrane. The hormone–
receptor complex activates a membrane protein called a G
protein. The activated G protein in turn activates adenylate
cyclase.
2. Adenylate cyclase converts ATP into cyclic AMP (cAMP).
Because the enzyme’s active site is on the inner surface of the
plasma membrane, this reaction occurs in the cytosol of the cell.
3. Cyclic AMP (the second messenger) activates one or more protein
kinases, which may be free in the cytosol or bound to the plasma
membrane. A protein kinase is an enzyme that phosphorylates
(adds a phosphate group to) other cellular proteins (such as
enzymes). The donor of the phosphate group is ATP, which is
converted to ADP.
20. 4. Activated protein kinases phosphorylate one or more
cellular proteins. Phosphorylation activates some of these
proteins and inactivates others, rather like turning a switch
on or off.
5. Phosphorylated proteins in turn cause reactions that produce
physiological responses. Different protein kinases exist
within different target cells and within different organelles
of the same target cell. Thus, one protein kinase might
trigger glycogen synthesis, a second might cause the
breakdown of triglyceride, a third may promote protein
synthesis, and so forth. As noted in step 4, phosphorylation
by a protein kinase can also inhibit certain proteins. For
example, some of the kinases unleashed when epinephrine
binds to liver cells inactivate an enzyme needed for
glycogen synthesis.
6. After a brief period, an enzyme called phosphodiesterase
inactivates cAMP. Thus, the cell’s response is turned off
unless new hormone molecules continue to bind to their
receptors in the plasma membrane.
21. Many hormones exert at least some of their physiological effects
through the increased synthesis of cAMP.
◦ Antidiuretic hormone (ADH)
◦ Thyroid-stimulating hormone (TSH)
◦ Adrenocorticotropic hormone (ACTH)
◦ Glucagon
◦ Epinephrine
◦ Hypothalamic releasing hormones
In other cases, the level of cyclic AMP decreases in response to the
binding of a hormone to its receptor.
◦ Growth hormone–inhibiting hormone (GHIH)
Besides cAMP, other second messengers include
◦ Calcium ions (Ca2+)
◦ cGMP (cyclic guanosine monophosphate)
◦ Inositol trisphosphate (IP3)
◦ Diacylglycerol (DAG)
23. IP3 mechanism
Hormone binds to a receptor in the cell membrane (step 1) and, via a G protein (step 2),
activates phospholipase C (step 3).
Phospholipase C liberates diacylglycerol and IP3 from membrane lipids (step 4).
IP3 mobilizes Ca2+ from the endoplasmic reticulum (step 5). Together, Ca2+ and
diacylglycerol activate protein kinase C (step 6), which phosphorylates proteins and
causes specific physiologic actions (step 7).
24. Ca2+ – calmodulin mechanism
Hormone binds to a receptor in the cell
membrane (step 1) and, via a G protein,
has two actions:
it opens cell membrane Ca2+
channels (step 2).
it releases Ca2+ from the
endoplasmic reticulum (step 2).
Together, these two actions produce an
increase in intracellular [Ca2+ ] (step 3).
Ca2+ binds to calmodulin (step 4), and the
Ca2+ –calmodulin complex produces
physiologic actions (step 5).
25. A given hormone may use different second messengers in different target
cells.
Hormones that bind to plasma membrane receptors can induce their effects
at very low concentrations because they initiate a cascade or chain reaction,
each step of which multiplies or amplifies the initial effect.
For example, the binding of a single molecule of epinephrine to its
receptor on a liver cell may activate a hundred or so G proteins, each of
which activates an adenylate cyclase molecule.
If each adenylate cyclase produces even 1000 cAMP, then 100,000 of these
second messengers will be liberated inside the cell.
Each cAMP may activate a protein kinase, which in turn can act on
hundreds or thousands of substrate molecules.
Some of the kinases phosphorylate and activate a key enzyme needed for
glycogen breakdown.
The end result of the binding of a single molecule of epinephrine to its
receptor is the breakdown of millions of glycogen molecules into glucose
monomers.
26. Hormone Interactions
The responsiveness of a target cell to a hormone
depends on
the hormone’s concentration in the blood
the abundance of the target cell’s hormone receptors
influences exerted by other hormones
27. A target cell responds more vigorously when the level of a hormone
rises or when it has more receptors (upregulation).
In addition, the actions of some hormones on target cells require a
simultaneous or recent exposure to a second hormone.
In such cases, the second hormone is said to have a permissive
effect.
For example, epinephrine alone only weakly stimulates lipolysis
(the breakdown of triglycerides), but when small amounts of thyroid
hormones (T3 and T4) are present, the same amount of epinephrine
stimulates lipolysis much more powerfully.
The permissive hormone
◦ Sometimes increases the number of receptors for the other hormone
◦ Sometimes it promotes the synthesis of an enzyme required for the
expression of the other hormone’s effects
28. When the effect of two hormones acting together is greater or more
extensive than the effect of each hormone acting alone, the two
hormones are said to have a synergistic effect.
For example, normal development of oocytes in the ovaries requires
both follicle stimulating hormone from the anterior pituitary and
estrogens from the ovaries.
Neither hormone alone is sufficient.
When one hormone opposes the actions of another hormone, the
two hormones are said to have antagonistic effects.
An example of an antagonistic pair of hormones is insulin, which
promotes synthesis of glycogen by liver cells, and glucagon, which
stimulates breakdown of glycogen in the liver.
29. Control of Hormone Secretion
Hormone secretion is regulated by
1. signals from the nervous system
2. chemical changes in the blood
3. other hormones
For example, nerve impulses to the adrenal medullae regulate
the release of epinephrine
Blood Ca2+ level regulates the secretion of parathyroid
hormone
A hormone from the anterior pituitary (adrenocorticotropic
hormone) stimulates the release of cortisol by the adrenal
cortex.
38. Human Growth Hormone and Insulin-like Growth
Factors
Somatotrophs are the most numerous cells in the anterior
pituitary.
Human growth hormone (hGH) is the most plentiful anterior
pituitary hormone.
The main function of hGH is to promote synthesis and
secretion of small protein hormones called insulin-like
growth factors (IGFs) or somatomedins.
In response to human growth hormone, cells in the liver,
skeletal muscles, cartilage, bones, and other tissues secrete
IGFs, which may either enter the bloodstream from the liver
or act locally in other tissues as autocrines or paracrines.
40. The functions of IGFs include the following:
IGFs cause cells to grow and multiply by increasing uptake
of amino acids into cells and accelerating protein synthesis.
IGFs also enhance lipolysis in adipose tissue, which results
in increased use of the released fatty acids for ATP production
by body cells.
In addition to this, human growth hormone and IGFs
influence carbohydrate metabolism by decreasing glucose
uptake, which decreases the use of glucose for ATP
production by most body cells. IGFs and human growth
hormone may also stimulate liver cells to release glucose into
the blood.
41. Somatotrophs in the anterior pituitary release bursts of
human growth hormone every few hours, especially
during sleep.
Their secretory activity is controlled mainly by two
hypothalamic hormones:
◦ Growth hormone–releasing hormone (GHRH) promotes
secretion of human growth hormone
◦ Growth hormone–inhibiting hormone (GHIH) suppresses it
42.
43. Solid arrows indicate stimulation of secretion, Dashed arrows indicate inhibition of secretion via negative
feedback.
44. A major regulator of GHRH and GHIH secretion is the blood glucose level:
1. Hypoglycemia, an abnormally low blood glucose concentration,
stimulates the hypothalamus to secrete GHRH, which flows toward the
anterior pituitary in the hypophyseal portal veins.
2. On reaching the anterior pituitary, GHRH stimulates somatotrophs to
release human growth hormone.
3. Human growth hormone stimulates secretion of insulinlike growth factors,
which speed breakdown of liver glycogen into glucose, causing glucose to
enter the blood more rapidly.
4. As a result, blood glucose rises to the normal level (about 90 mg/100 mL
of blood plasma).
5. An increase in blood glucose above the normal level inhibits release of
GHRH.
6. Hyperglycemia, an abnormally high blood glucose concentration,
stimulates the hypothalamus to secrete GHIH (while inhibiting the
secretion of GHRH).
7. On reaching the anterior pituitary in portal blood, GHIH inhibits secretion
of human growth hormone by somatotrophs.
8. A low level of human growth hormone and IGFs slows breakdown of
glycogen in the liver, and glucose is released into the blood more slowly.
9. Blood glucose falls to the normal level.
10. A decrease in blood glucose below the normal level (hypoglycemia)
inhibits release of GHIH.
45. Actions of Thyroid Hormones
Because most body cells have receptors for thyroid hormones, T3 and
T4 exert their effects throughout the body.
1. Thyroid hormones increase basal metabolic rate (BMR), the rate of
oxygen consumption under standard or basal conditions, by
stimulating the use of cellular oxygen to produce ATP. When the basal
metabolic rate increases, cellular metabolism of carbohydrates, lipids,
and proteins increases.
2. A second major effect of thyroid hormones is to stimulate synthesis of
additional sodium–potassium pumps (Na+/K+ ATPase), which use
large amounts of ATP to continually eject sodium ions from the
cytosol into the extracellular fluid and potassium ions from the
extracellular fluid into the cytosol. As cells produce and use more
ATP, more heat is given off, and body temperature rises. This
phenomenon is called the calorigenic effect. In this way, thyroid
hormones play an important role in the maintenance of normal body
temperature.
46. 3. In the regulation of metabolism, the thyroid hormones stimulate
protein synthesis and increase the use of glucose and fatty acids for
ATP production. They also increase lipolysis and enhance
cholesterol excretion, thus reducing blood cholesterol level.
4. The thyroid hormones enhance some actions of the catecholamines
(norepinephrine and epinephrine) because they up-regulate beta (β)
receptors. For this reason, symptoms of hyperthyroidism include
increased heart rate, more forceful heartbeats, and increased blood
pressure.
5. Together with human growth hormone and insulin, thyroid
hormones accelerate body growth, particularly the growth of the
nervous and skeletal systems. Deficiency of thyroid hormones
during fetal development, infancy, or childhood causes severe
mental retardation and stunted bone growth.
Conditions that increase ATP demand - a cold environment,
hypoglycemia, high altitude, and pregnancy—also increase the
secretion of the thyroid hormones.
48. Control of thyroid hormone secretion.
T3 = triiodothyronine; T4 = thyroxine; TRH = thyrotropin-releasing hormone; TSH =
thyroid stimulating hormone.
49. Actions of Thyroid Hormones:
Increase basal metabolic rate
Stimulate synthesis of Na+/K+ ATPase
Increase body temperature (calorigenic
effect)
Stimulate protein synthesis
Increase the use of glucose and fatty
acids for ATP production
Stimulate lipolysis
Enhance some actions of
catecholamines
Regulate development and growth of
nervous tissue and bones
50. Control of Thyroid Hormone Secretion
Thyrotropin-releasing hormone (TRH) from the hypothalamus
and thyroid-stimulating hormone (TSH) from the anterior
pituitary stimulate synthesis and release of thyroid hormones,
as shown in the figure:
1. Low blood levels of T3 and T4 or low metabolic rate stimulates
the hypothalamus to secrete TRH.
2. TRH enters the hypophyseal portal veins and flows to the anterior
pituitary, where it stimulates thyrotrophs to secrete TSH.
3. TSH stimulates virtually all aspects of thyroid follicular cell
activity, including iodide trapping, hormone synthesis and
secretion and growth of the follicular cells.
4. The thyroid follicular cells release T3 and T4 into the blood until
the metabolic rate returns to normal.
5. An elevated level of T3 inhibits release of TRH and TSH
(negative feedback inhibition).
51. Calcitonin
The hormone produced by the parafollicular cells of the
thyroid gland is calcitonin (CT).
CT can decrease the level of calcium in the blood.
The secretion of CT is controlled by a negative feedback
system.
When its blood level is high, calcitonin lowers the amount of
blood calcium and phosphates
◦ by inhibiting bone resorption (breakdown of bone extracellular
matrix) by osteoclasts
◦ by accelerating uptake of calcium and phosphates into bone
extracellular matrix.
52. The roles of calcitonin (green arrows), parathyroid hormone (blue arrows), and calcitriol (orange
arrows) in calcium homeostasis.
53. The blood calcium level directly controls the secretion of both
calcitonin and parathyroid hormone via negative feedback loops that
do not involve the pituitary gland:
1. A higher-than-normal level of calcium ions (Ca2+) in the blood stimulates
parafollicular cells of the thyroid gland to release more calcitonin.
2. Calcitonin inhibits the activity of osteoclasts, thereby decreasing the
blood Ca2+ level.
3. A lower-than-normal level of Ca2+ in the blood stimulates chief cells of
the parathyroid gland to release more PTH.
4. PTH promotes resorption of bone extracellular matrix, which releases
Ca2+ into the blood and slows loss of Ca2+ in the urine, raising the blood
level of Ca2+.
5. PTH also stimulates the kidneys to synthesize calcitriol, the active form
of vitamin D.
6. Calcitriol stimulates increased absorption of Ca2+ from foods in the
gastrointestinal tract, which helps increase the blood level of Ca2+.
56. Glucocorticoids
The glucocorticoids, which regulate metabolism and resistance to stress,
include
◦ Cortisol (also called hydrocortisone)
◦ Corticosterone
◦ Cortisone
Of these three hormones secreted by the zona fasciculata, cortisol is the most
abundant, accounting for about 95% of glucocorticoid activity.
Control of glucocorticoid secretion occurs via a typical negative feedback
system.
Low blood levels of glucocorticoids, mainly cortisol, stimulate neurosecretory
cells in the hypothalamus to secrete corticotropin-releasing hormone
(CRH).
CRH (together with a low level of cortisol) promotes the release of ACTH
from the anterior pituitary. ACTH flows in the blood to the adrenal cortex,
where it stimulates glucocorticoid secretion.
57. Control of glucocorticoid secretion.
ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone.
58. Glucocorticoids have the following effects:
Protein breakdown.
Glucocorticoids increase the rate of protein breakdown, mainly in
muscle fibers, and thus increase the liberation of amino acids into
the bloodstream. The amino acids may be used by body cells for
synthesis of new proteins or for ATP production.
Glucose formation.
On stimulation by glucocorticoids, liver cells may convert certain
amino acids or lactic acid to glucose, which neurons and other cells
can use for ATP production. Such conversion of a substance other
than glycogen or another monosaccharide into glucose is called
gluconeogenesis.
Lipolysis.
Glucocorticoids stimulate lipolysis, the breakdown of triglycerides
and release of fatty acids from adipose tissue into the blood.
59. Resistance to stress.
Glucocorticoids work in many ways to provide resistance to stress.
The additional glucose supplied by the liver cells provides tissues
with a ready source of ATP to combat a range of stresses, including
exercise, fasting, fright, temperature extremes, high altitude,
bleeding, infection, surgery, trauma, and disease. Because
glucocorticoids make blood vessels more sensitive to other hormones
that cause vasoconstriction, they raise blood pressure. This effect
would be an advantage in cases of severe blood loss, which causes
blood pressure to drop.
Anti-inflammatory effects.
Glucocorticoids inhibit white blood cells that participate in
inflammatory responses. Unfortunately, glucocorticoids also retard
tissue repair, and as a result, they slow wound healing. Although high
doses can cause severe mental disturbances, glucocorticoids are very
useful in the treatment of chronic inflammatory disorders such as
rheumatoid arthritis.
Depression of immune responses.
High doses of glucocorticoids depress immune responses. For this
reason, glucocorticoids are prescribed for organ transplant recipients
to retard tissue rejection by the immune system.
60.
61. Pancreatic Islets
Regulation of Glucagon and Insulin Secretion
The principal action of glucagon is to increase blood
glucose level when it falls below normal.
Insulin, on the other hand, helps lower blood glucose
level when it is too high.
The level of blood glucose controls secretion of
glucagon and insulin via negative feedback
62.
63.
64. 1. Low blood glucose level (hypoglycemia) stimulates secretion of
glucagon from alpha cells of the pancreatic islets.
2. Glucagon acts on hepatocytes (liver cells) to accelerate the
conversion of glycogen into glucose (glycogenolysis) and to
promote formation of glucose from lactic acid and certain amino
acids (gluconeogenesis).
3. As a result, hepatocytes release glucose into the blood more
rapidly, and blood glucose level rises.
4. If blood glucose continues to rise, high blood glucose level
(hyperglycemia) inhibits release of glucagon (negative feedback).
65. 5. High blood glucose (hyperglycemia) stimulates secretion of
insulin by beta cells of the pancreatic islets.
6. Insulin acts on various cells in the body to accelerate facilitated
diffusion of glucose into cells; to speed conversion of glucose into
glycogen (glycogenesis); to increase uptake of amino acids by
cells and to increase protein synthesis; to speed synthesis of fatty
acids (lipogenesis); to slow the conversion of glycogen to glucose
(glycogenolysis); and to slow the formation of glucose from lactic
acid and amino acids (gluconeogenesis).
7. As a result, blood glucose level falls.
8. If blood glucose level drops below normal, low blood glucose
inhibits release of insulin (negative feedback) and stimulates
release of glucagon.
