1.
Which of the following statements best describe the factor(s) regulating insulin secretion?
Correct Answer
A. Calcium-dependent event.
Explanation
Feedback: Insulin secretion is a 7-step process that requires a calcium flux. An influx of calcium
causes migration of the granules containing insulin (and C-peptide) to migrate to the membrane and
undergo exocytosis.
Distracter explanations:
Glucose uptake in the pancreatic beta cells is via GLUT-2, not GLUT-4. Recall that GLUT-4 is
expressed predominantly in skeletal muscle and adipose tissue.
There is no evidence to suggest that insulin secretion is dependent or regulated by glucagon.
On the other hand, there is some evidence to suggest that insulin may play a role in regulating
the release of glucagon from the alpha cells.
Insulin secretion is not stimulated during exercise, insulin secretion is dampened or inhibited
during exercise.
Insulin secretion is triggered by glucose concentrations above 8-10 mM or when there is a
rapid increase of 2mM or more (e.g. glucose concentrations increases from 5 to 7 mM rapidly).
Glucagon secretion is stimulated when glucose concentration drop below 4 mM or when there
is a rapid drop of 2 mM or greater
2.
Glucose uptake is facilitated via the membrane-bound glucose transporters (GLUTs). Glucose
uptake in hepatocytes is regulated primarily by which of the following GLUTs?
Correct Answer
B. GLUT-2
Explanation
Feedback: Glucose uptake in hepatocytes and pancreatic beta cells occurs via the GLUT-2
transporter. The GLUT-2 transporter is regulated predominantly by the hepatocyte growth factor
(HGF) cMET pathway, not by insulin. Note that the brain and nervous tissues express several
members of the GLUT family, but do not express GLUT-2 and GLUT-4.
Distracter explanations:
GLUT-1 facilitates glucose transport across the blood brain barrier and is localized to most
tissues throughout the body, but is not the primary GLUT in pancreatic beta cells, hepatocytes,
adipocytes or skeletal muscle.
GLUT-3 and GLUT-5 are predominantly localized to reproductive tract tissues and/or gametes.
Some evidence also suggests GLUT-3 is the primary mechanism for glucose uptake in
neurons.
GLUT-4 is localized predominantly in skeletal muscle and adipose tissue.
GLUT-6 was originally described as GLUT-9, functions to facilitate glucose uptake in the brain,
spleen and leukocytes.
3.
Which of the following biomolecules exerts long-loop positive feedback on the hypothalamus?
Correct Answer
B. Estradiol
Explanation
Feedback: Estradiol exerts long-loop positive feedback to stimulate the release of GnRH during the
late-proliferative phase of the menstrual cycle before ovulation. Estradiol exerts long-loop negative
feedback during the early- and mid-proliferative phase, and also throughout the secretory phase of
the menstrual cycle (which is predominated by progesterone).
Distracter explanations:
Cortisol exerts long-loop negative feedback. During the “Flight or Fight” response cortisol does
not stimulate more CRH – CRH stimulates the release of more CRH, which overrides the
negative effects of increased negative cortisol feedback.
Growth Hormone, from the anterior pituitary, exerts short-loop negative feedback on the
hypothalamus.
Insulin is stimulated by glucose concentration, and may exert some feedback on the
hypothalamus (e.g. is can suppress the release of GHRH), but it does not exert long-loop
positive feedback. Additionally, this would not be viewed as classic feedback, but rather as
end-product feedback (similar to calcium levels regulating PTH).
Progesterone, secreted primarily from the corpus luteum and the placenta, always exerts longloop
negative feedback on the hypothalamus. Progesterone negative feedback is the basis for
progesterone-only contraceptives.
Thyroxine, from the thyroid gland, exerts long-loop negative feedback
4.
Which of the following pituitary hormones is regulated by a statin and liberin?
Correct Answer
B. GH
Explanation
Feedback: Growth hormone (GH), released from the anterior pituitary, is under the dual regulation of
the stimulatory Growth hormone releasing hormone (GHRH) and the inhibitory somatostatin (SRIF).
Recall that liberins (e.g. GHRH) are released from the hypothalamus to stimulate the production
and/or release of an anterior pituitary hormone, whereas statins (e.g. SRIF) are released from the
hypothalamus to inhibit the production/release of an anterior pituitary hormone.
Distracter explanations:
Follicle stimulating hormone (FSH) and luteinizing hormone (LH) are stimulated by
gonadotropin releasing hormone (GnRH), which is a liberin.
Thyroid stimulating hormone (TSH) is regulated by thyroid releasing hormone (TRH), which is
a liberin.
Prolactin (PRL) is under the tonic inhibitory control of dopamine (DA), which is a statin.
5.
Synthetic somatostatin analogues, such as octreotide, exert inhibitory functions on several tissues
throughout the body. Octreotide would exert the most beneficial physiological effects in a 25-yearold
patient with which of the following problems?
Correct Answer
A. Acromegaly
Explanation
Feedback: Recognize that acromegaly is disregulated release of growth hormone (GH) from the
pituitary, resulting in increased growth during adulthood. Endogenous levels of GH are elevated, due
to decreased levels of somatostatin (SRIF). Octreotide replacement therapy is used to increase the
inhibitory actions of SRIF, to decrease GH and control growth rate.
Distracter explanations:
Large levels of SRIF inhibit the release of insulin, and therefore SRIF analogues would not be
used in people with either Type 1 or Type 2 Diabetes.
Women with polycystic ovary syndrome (PCOS) are at risk for developing insulin resistance
and often have impaired metabolic function, but to date no studies have linked SRIF with
PCOS.
Large doses of SRIF have been shown to inhibit insulin and glucagon, and therefore SRIF
analogues would not be used in patients exhibiting abnormally low glucagon secretion.
6.
Which of the following favorable characteristics promote the use of C-peptide as a marker for
determining insulin resistance and/or glucose homeostasis? (Mark ALL that apply)
Correct Answer(s)
A. Metabolized by the kidney.
E. Long half-life compared with insulin.
Explanation
Feedback: C-peptide is also call the “C-chain”, and is stored in insulin-containing vesicles in the
pancreatic beta cells. The half-life of C-peptide is ~20-30 minutes, compared with the relatively short
half-life of insulin (~5 min). C-peptide is metabolized predominantly by the kidney, which contributes
to the longer half-life. Approximately 75% of the insulin secreted from the beta cells is metabolized by
the liver on the first-past effect – which contributes to insulin’s shorter half-life.
Distracter explanations:
C-peptide is released with insulin in response to elevated glucose, and therefore is not
secreted in a pulsatile manner. The release of insulin and C-peptide granules is considered
‘episodic release’.
The interactions of albumin with C-peptide and insulin are under investigation, to determine if
albumin conjugates can be used for insulin replacement therapy.
C-peptide is proteolytic product of proinsulin processing, is synthesized and stored in granules
in the pancreatic beta cells, not alpha cells.
7.
Reductions in which of the following proteins will cause the greatest decrease in adrenal steroid
production? (Mark ALL that apply)
Correct Answer(s)
D. CYP11
F. StAR Protein
Explanation
Feedback: Steroidogenic acute regulatory (StAR) protein shuttles cholesterol across the outer
mitochondrial membrane to the inner mitochondrial membrane, where the cytochrome enzymes
reside. CYP11, also known as P450 side chain cleavage or 20-22 desmolase, resides on the inner
mitochondrial membrane and converts cholesterol to pregnenolone. Reduced levels of either StAR or
CYP11 will drastically reduce steroid production in the adrenal gland.
Distracter explanations:
CYP19 is also known as aromatase, and converts androgens to estrogens. This is one of the
final stages of steroid production, and will not affect adrenal steroid production.
11-Hydroxylase, 17-Hydroxylase, and 21-Hydroxylase are essential for production of the
adrenal steroid hormones. However, CYP11A and StAR protein regulate the production of
pregnenolone, which is the precursor for all steroids, and therefore reductions in CYP11A will
result in reduced steroid production.
Note: CYP11A and CYP11B (11-hydroxylase) both reside in the mitochondria in the adrenal gland
8.
Which of the following hormones has the longest half-life in serum?
Correct Answer
E. Growth Hormone
Explanation
Feedback: The active half-life of native growth hormone (GH) is only 20-30 minutes in serum, but
the circulating half-life of GH is 10-16 hrs. The circulating half-life of GH is drastically increased due
to GH binding with growth hormone binding protein (GHBP), the soluble portion of the GH receptor.
Distracter explanations:
Angiotensin II and Epinephrine each have a half-life of ~2 min, and therefore these hormones
have the shortest half-life of the biomolecules listed.
The half-life of insulin is 3-10 min.
The half-life of prostaglandin F2 is approximately 5-30 minutes, depending on the site of
production.
The half life of aldosterone and cortisol are approximately 30-60 minutes.
9.
Which of the following best describes the secretion pattern(s) of adrenocorticotropic hormone
(ACTH) in adults?
Correct Answer
G. Circadian, Pulsatile and Episodic
Explanation
Feedback: Many of the hormones released from the anterior pituitary are release in pulsatile manner
in response to the hypothalamic releasing factors. Most of the anterior pituitary hormones, including
ACTH, also exhibit a circadian rhythm, exhibiting a peak and nadir each day. ACTH is unique, in that
the ‘Fight or Flight’ response can cause an episodic release of CRH, leading to an episodic release of
ACTH.
Distracter explanations:
Circadian refers to a daily rhythm or daily pattern, with the hormones exhibiting a peak and
nadir each day. ACTH and GH both exhibit circadian patterns.
Pulsatile refers to pulsatile release of a hormone throughout the day. All of the anterior
pituitary hormones (LH, FSH, GH, ACTH, TSH and PRL) exhibit some pattern of pulsatile
release throughout the day.
Episodic release refers to release of a hormone in response to a specific stimuli. The classic
example of episodic release is insulin release in response to elevated blood glucose.
10.
An 18-year old man displays gigantism. Functional MRI indicates the hypothalamus and pituitary
gland are of normal size. Which of the following hormones was most likely reduced in this patient
when he was a young boy?
Correct Answer
F. Somatostatin
Explanation
Feedback: Gigantism is very rare and has two primary causes: congenital which leads to
physiological disruption of the hypothalamic-pituitary system. This condition results in decreased
somatostatin (SRIF), increased growth hormone releasing hormone (GHRH) and elevated GH. The
other half of the cases are due to a pituitary tumor which oversecretes GH and causes excessive
growth. High levels of GH actually decrease GHRH and stimulate SRIF, in an attempt to turn off the
pituitary – but because the tumor is hypersecreting GH, the pituitary cannot respond and continues to
secrete high levels of GH. Regardless of the cause, gigantism is the result of increased and
prolonged levels of GH throughout childhood, especially during puberty when growth rate is maximal.
Distracter explanations:
Growth hormone (GH), growth hormone releasing hormone (GHRH), insulin-like growth factor
1 (IGF1) and insulin-like growth factor 2 (IGF2) would all be increased in this man when he
was a young boy.
Insulin would still be secreted in an episodic manner in response to blood glucose, and
baseline levels of insulin would be normal unless there was an underlying (and additional)
metabolic problem.
11.
Which of the following biomolecules is the most sensitive and useful for clinically diagnosing
thyroid function?
Correct Answer
C. Thyroid Stimulating Hormone (TSH)
Explanation
Feedback: Thyroid stimulating hormone (TSH) is recognized as the most sensitive marker for thyroid
function. TSH levels must be compared with the relative levels of both T4 and T3 to determine the
primary source of the problem – but 90% of all thyroid problems are due to an abnormal thyroid
gland, not the hypothalamic-pituitary axis. For example, primary hyperthyroidism is due to the thyroid
gland, and Grave’s disease accounts for ~90% of all cases. Secondary hyperthyroidism – where T3,
T4 and TSH are elevated, indicate a non-responsive hypo-pit axis – but only account for ~10% of all
thyroid problems.
Distracter explanations:
Thyroid binding globulin may be measured to insure the amount of free thyroid hormone in the blood,
but is not considered a sensitive assay.
TRH is released into the portal blood and is not measured.
T3 and T4 must also be measured to determine thyroid gland function. However, the levels of T4 and
T3 only indicate the relative function of the thyroid gland – the levels of TSH indicate the source of the
problem, therefore TSH is considered more sensitive and clinically useful (but recognize levels of T4
and T3 are also clinically important and are the first indication of an abnormally functioning thyroid
gland).
12.
Thyroid hormone stimulates thermogenesis primarily in which of the following tissues?
Correct Answer
A. Adipose
Explanation
Feedback: Thyroid hormones regulate thermogenesis in adipose tissue, predominantly brown
adipose tissue (BAT), by regulating the production of thermogenin, otherwise known as uncoupling
protein 1 (UCP-1). Catecholamines trigger protein kinase activation, which leads to increased
production of lipase and the release of free fatty acids. The free fatty acids cross into the
mitochrondria. The hydrogen atoms, releases as part of the electron transport process, are then
shuttled through the UCP-1 complex to generate heat. Approximately 20% of the hydrogen atoms
are shuttled through the ATPase, to maintain adequate amounts of energy so the cells can maintain
or increase thermogenesis. BAT thermogenesis occurs primarily in infants after birth.
Distracter explanations:
Minor amount of heat production may occur in liver and skeletal muscle when glycogen stores
are mobilized – but not a major source of heat production.
Brain and cardiac muscle do not exhibit thermogenesis, but benefit directly from the increased
heat. The thermoregulatory center of the brain also is the primary site that regulates body
temperature under normal physiological states, and predominates thermoregulation activities
in adults.
13.
A pharmaceutical company develops a new glucocorticoid receptor antagonist. In vivo studies
performed in wild-type mice (i.e. normal controls) suggest this compound also binds with
additional steroid receptors. Based on the general principals of receptor homology, this
compound most likely interacts with which of the following steroid receptors?
Correct Answer
D. Mineralocorticoid Receptor
Explanation
Feedback: The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) exhibit a high
homology in both the DNA binding domain and ligand binding domain regions. Thus, MR is the most
likely receptor interaction with the GR antagonists.
Distracter explanations:
The antagonist may also interact with the progesterone receptor (PR), which also shares a
high degree of homology with the corticoid receptors. This has been observed in real-life –
Mifepristone (RU-486) was developed as a GR antagonist, but was found to exhibit a higher
affinity for the PR. You could have also chosen this as a correct answer.
The androgen receptor has an ~50% homology with corticoid receptors, and therefore some
cross-reactive binding may occur. Although the AR and corticoid receptors exhibit lower
homology than GR/MR with PR, you could also argue that this answer may be possible and
therefore also correct.
The estrogen receptors (ERs) exhibit a low homology with any of the other receptors, and
therefore the antagonist would likely not interact with the ERs. These are the only true ‘wrong’
answers to this question.
14.
Which of the following biomolecules binds to a nuclear receptor and directly regulates gene
transcription?
Correct Answer
B. Calcitriol
Explanation
Feedback: Calcitriol is the active metabolite of Vitamin D. Recall that steroid hormones, thyroid
hormones, Vit D and Vit A all bind with nuclear (i.e. intracellular) receptors. Calcitriol has recently
been shown to regulate approximately 800 genes in man.
Distracter explanations:
The other ligands bind to membrane-bound receptors, stimulate second-messenger signaling
cascade, and therefore indirectly regulate gene transcription.
Insulin and insulin-like growth factor bind to heterotetramer membrane-bound receptors (IGF
Type 2 receptor is a monomer/dimer hybrid).
Growth hormone binds to a membrane-bound monomer that quickly forms an active dimer
receptor
Angiotensin II binds to a G-protein coupled membrane-bound receptor.
15.
Which of the following hormones is synthesized in the hypothalamus and secreted from the
pituitary?
Correct Answer
B. Antidiuretic Hormone
Explanation
Feedback: Antidiuretic hormone (ADH, also known as vasopressin) and oxytocin are nonapeptides
that are synthesized in hypothalamic neurons. These peptides then migrate along the nerve axis to
the neuron terminals, which reside in the posterior pituitary. The peptides are then stored in secretory
vesicles and released upon stimulation. Oxytocin is predominantly released due to neural reflex arcs,
stimulated by nerve endings in the myometrium and breast.
Distracter explanations:
Adrenocorticotropic hormone (ACTH), follicle stimulating hormone (FSH), growth hormone
(GH) and prolactin (PRL) are all synthesized and stored in their respective cells within the
anterior pituitary.
Production and secretion of these hormones are regulated by the liberins and statins produced
in the hypothalamus and then subsequently released into the portal circulation. The liberins
and statins then bind to specific receptors in the pituitary to regulate production of ACTH, FSH,
GH and PRL, respectively.
16.
A 65-year-old woman, recovering from a bacterial infection after visiting the island of Guadeloupe,
suddenly develops severe nausea and vomiting. The woman is rushed to the emergency room. The
patient is confused and cannot answer basic questions – she does not remember her age. Blood
pressure is 90/55 and the patient is severely dehydrated.
This woman is diagnosed with which of the following disorders?
Correct Answer
A. Adrenal crisis
Explanation
Feedback: This patient’s symptoms are consistent with sudden onset adrenal failure, also termed
‘Adrenal Crisis’ or ‘Addisonian Crisis’. This is the acute withdrawal of corticoid hormone production,
which can quickly lead to shock and subsequent death if not treated immediately.
Distracter explanations:
Adrenal Disease refers to chronic onset, and Adrenal Syndrome refers to general adrenal
insufficiency before the cause can be determined.
Primary insufficiency occurs when levels of ACTH are normal but the adrenal gland does not
respond accordingly.
Secondary and tertiary adrenal insufficiency indicate inadequate amounts of ACTH.
Tertiary is often attributed to decreased production of CRH. CRH is a unique hypothalamic
releasing hormone, in that CRH binds to serum proteins and can be measured in serum.
However, the measurements are often inprecise, the assay is expensive, and oftentimes it is
irrelevant because the result is still reduced ACTH.
Adrenal crisis is often due to primary adrenal insufficiency – but without levels of ACTH to
determine the source of the problem, this is not the correct answer.
17.
A 65-year-old woman, recovering from a bacterial infection after visiting the island of Guadeloupe,
suddenly develops severe nausea and vomiting. The woman is rushed to the emergency room. The
patient is confused and cannot answer basic questions – she does not remember her age. Blood
pressure is 90/55 and the patient is severely dehydrated.
Which of the following hormones is most likely decreased in this patient and the cause of her
symptoms and signs?
Correct Answer
C. Cortisol
Explanation
Feedback: Low levels of cortisol are the primary problem. Recall that cortisol acts throughout the
body. Cortisol binds with the corticoid receptor to directly regulate gene transcription, and cortisol is a
permissive hormone that augments the actions of many hormones throughout the body. Both cortisol
and thyroid hormones are permissive hormones that are required to maintain homeostasis.
Distracter explanations:
Angiotensin II is produced in the lungs and is not dependent on the adrenal. Levels will likely
rise in an attempt to increase aldosterone production, which in itself can cause severe
problems, because ANG II is a powerful vasoconstrictor.
Renin is released by the kidney, not the adrenal gland.
Corticosterone is primarily converted, and is not the active metabolite.
Aldosterone levels will also fall, but the primary cause for this patient’s problems are due to the
rapid withdrawal of cortisol. Mineralocorticoid therapy will begin once the patient is stabilized.
18.
A 22-year-old man presents with acute onset of severe aldosterone deficiency. The patient’s
cortisol levels are normal. Which of the following biomolecules is most likely reduced in this
patient?
Correct Answer
D. Angiotensin II
Explanation
Feedback: Recognize that aldosterone production is regulated by angiotensin II and blood pressure.
The patient’s cortisol levels are normal – which indicates that the majority of the adrenal steroidogenic
enzymes are produced and active, which indicates that levels of adrenocorticotropic hormone levels
are likely adequate. Recall that ACTH regulates the expression of the rate-limiting enzymes, CYP11
and StAR, whereas ANG II regulates aldosterone synthase.
Distracter explanations:
Cortisol levels are normal which indicates ACTH levels are most likely not reduced.
Angiotensinogen and ANG I are precursors for ANG II – but these biomolecules are not
biologically inactive. You cannot determine from the information provided that levels of
angiotensinogen or ANG II are abnormal.
Renin is produced by the kidney and convert angiotensinogen to ANG 1, and may be
abnormal, but you cannot determine if levels of ANG I are reduced, because ANG I is (for the
most part) biologically inactive.
19.
A 46-year-old woman complains of weight gain. History reveals sudden onset of hot flashes and
amenorrhea for 11 months. Physical exam reveals engorged and tender breasts; otherwise
unremarkable.
Which of the following biomolecules is most likely elevated in this patient?
Correct Answer
D. Prolactin
Explanation
Feedback: Physical exam reveals engorged and tender breasts, which is attributed to high levels of
prolactin. The woman has not had a menstrual period for 11 months, and therefore she is not
pregnant or breastfeeding. The woman is exhibiting symptoms associated with hyperprolactinemia,
most likely caused by hypothyroidism.
Distracter explanations:
Levels of cortisol may be elevated and this woman may be stressed, but the primary hormone
stimulating breast development is prolactin, not cortisol.
FSH acts on the ovary and therefore would not cause these effects. This woman could be
exhibiting menopause symptoms, which will result in elevated FSH – but FSH has no known
affects on the mammary glands.
GH may stimulate breast development, but would not cause hot flashes.
This woman most likely also has hyperthyroidism – however, the increased prolactin is due to
an interaction with TRH on the pituitary lactotrophs. TSH would has no known effects on the
mammary glands.
20.
A 46-year-old woman complains of weight gain. History reveals sudden onset of hot flashes and
amenorrhea for 11 months. Physical exam reveals engorged and tender breasts; otherwise
unremarkable.
Reduced levels of which of the following hormones is the most likely cause of this patient’s
symptoms and signs?
Correct Answer
B. Dopamine
Explanation
Feedback: Prolactin is under the tonic inhibitory control of dopamine (DA). Reduced dopamine will
result in increased prolactin levels. Reductions in the other hormones have no established effects on
the production and/or secretion of prolactin.
Distracter explanations:
Cortisol is a red herring and should be omitted.
Oxytocin is released during suckling to contract the muscle cells lining the mammary ducts, thereby
stimulating milk ejection. Oxytocin is released in episodic spurts, and may be elevated in this patient,
not reduced.
Somatostatin levels are likely normal or may be slightly elevated in this patient, due to the decreased
metabolic rate – again, this patient is most likely also hypothyroid.
TRH is most likely increased, not decreased.
21.
A 46-year-old woman complains of weight gain. History reveals sudden onset of hot flashes and
amenorrhea for 11 months. Physical exam reveals engorged and tender breasts; otherwise
unremarkable.
This patient is most likely diagnosed with which of the following disorder(s)?
Correct Answer
F. Hypothyroidism
Explanation
Feedback: This patient is exhibiting classic signs of hypothyroidism, which affects a greater number
of women than men. Women with hypothyroidism often exhibit weight gain, irregular menstrual
cycles, and thermoregulatory problems. It is now recognized that women starting the menopausal
transition and afflicted with hypothyroidism often exhibit hot flashes. You should be able to clearly
identify/describe why the other distracters are not correct.
22.
A 41-year-old man is on safari in African plains when he gets separated from his safari guides and
becomes lost. The man has a 2 L bottle of clean water and no available food sources.
After 8 hrs without food the man feels hungry. Which of the following hormones is most likely
elevated and stimulates this man’s appetite and urge to eat?
Correct Answer
E. Neuropeptide Y
Explanation
Feeback: Neuropeptide Y is a potent orixegen, i.e. a biomolecule that stimulate’s appetite and food
intake. Ghrelin is released by the stomach in response to hunger, binds to the Ghrelin receptor in the
arcuate nucleus and stimulates the release of NPY.
Distracter explanations:
Cortisol does not play a role in short-term hunger. Cortisol may augment the actions of NPY
and Ghrelin in fasting or acute starvation states.
Ghrelin is released in response to hunger to stimulate eating – but does so by releasing NPY.
NPY directly stimulates appetite and food intake. You could argue that Ghrelin could also be
considered a correct answer – but recognize that NPY is the best answer.
GH is released in response to Ghrelin and NPY, but does not directly stimulate appetite or food
intake.
Leptin will be released by adipocytes after feeding to suppress the release of NPY. Leptin may
stimulate appetite and food intake during starvation states, as an adipocyte pro-survival
mechanism – but there is not enough date to clearly demonstrate this proposition.
23.
A 41-year-old man is on safari in African plains when he gets separated from his safari guides and
becomes lost. The man has a 2 L bottle of clean water and no available food sources.
The man does not find food and goes 5 days without eating. Which of the following hormones is
most likely elevated and stimulating glycogenolysis of this man’s liver glycogen stores?
Correct Answer
C. Glucagon
Explanation
Feedback: Glucagon will be released to stimulate glycogenolysis of glycogen stores, and to
stimulate hepatic gluceoneogensis. Glucagon secretion will be enhanced by continued
hypoglycemia.
Distracter explanations:
Cortisol levels will likely rise in response to continued stress. Cortisol will exert permissive
effects and stimulate protein catabolism. Cortisol will also stimulate production of glucagon
receptors, to stimulate glucagon’s glycogenolytic effects.
GLP-1 and GIP may stimulate glucagon release, but the incretins do not directly regulate
glycogenolysis.
Insulin will be released to facilitate glucose uptake in cells and tissues, but will not be elevated
to stimulate glycogenolysis.
24.
A 41-year-old man is on safari in African plains when he gets separated from his safari guides and
becomes lost. The man has a 2 L bottle of clean water and no available food sources.
The man remains lost and begins to feel fatigued and very weak. He is able to find water but has
found no food – he has been starving for 14 days. Which of the following biomolecules is most
likely reduced in this man?
Correct Answer
C. Growth Hormone Releasing Hormone
Explanation
Feedback: Growth hormone will be released for the first 5-7 days of acute starvation, to stimulate
glycogenolysis and inhibit glucose uptake by skeletal muscles. However, this man is now suffering
with chronic starvation, and the prolonged high levels of GHRH will result in an ultra-short negative
feedback loop – resulting in GHRH inhibiting its own release from the hypothalamus.
Distracter explanations:
Cortisol levels will remain elevated, in an attempt to return the man to metabolic homeostasis.
Ghrelin levels will remain elevated (as demonstrated in animal studies), but the constant
exposure to high Ghrelin levels causes desensitization and down-regulation of the Ghrelin
receptor.
As note in a previous answer, as lipolysis continues leptin will continue to be released in high
levels. Leptin may actually stimulate appetite during chronic starvation.
NPY levels will also remain high – but the NPY receptor will down-regulate. Note that high
levels of NPY may reach the systemic circulation, which may result in adverse affects on
cardiovascular health.
25.
Glucagon secretion is inhibited by which of the following biomolecules? (Mark ALL that apply)
Correct Answer(s)
D. High concentrations of Insulin.
E. High concentrations of Glucagon-like peptide 1 (GLP-1).
F. High concentrations of Glucose.
Explanation
Feedback: Glucagon secretion is regulated predominantly by glucose concentration, and high levels
of glucose are known to inhibit the secretion of glucagon from the pancreatic alpha cells. However,
the question did not ask for the primary regulator.
High levels of insulin are released in response to hyperglycemia, and insulin also can inhibit
glucagon. GLP-1, an incretin released from L-cells, can also inhibit the release of glucagon. The
effects of GLP-1 and insulin are – for the most part – likely indirect. The functionality of the insulin
receptor on the pancreatic alpha cells is not clear, and GLP-1 receptors are largely not expressed on
the alpha cells. Some recent reports have detected very low levels of GLP receptors mRNA in alpha
cells (~ 0.2% of the mRNA level found in beta cells), and localization studies using
immunocytochemistry have largely been unable to clearly demonstrate the presence of the GLP
receptors on the beta cells.
Distracter explanations:
Low concentration of glucose (below 4 mM) is the primary stimulus to stimulate glucagon
release.
There is no evidence to suggest that low concentrations of insulin or GLP-1 will inhibit
glucagon secretion.
High levels of insulin and GLP-1 are released in response to a meal and increased glucose
concentration; both proteins in high levels have been shown to inhibit glucagon release, largely
by indirect mechanisms.