Endocrine Physiology Flashcards
1
Q
What are the two main types of hormone signaling based on their receptor activation?
A
Hormones that activate plasma membrane receptors and hormones that activate intracellular receptors
2
Q
List the classic endocrine glands.
A
- Heart
- Kidney
- Adipose tissue
- Stomach
- Intestines
3
Q
What are the chemical structures of hormones?
A
- Protein or Peptide
- Amino acid derivatives (amines)
- Steroids
- Fatty acid derivatives
- Gases
4
Q
Define water-soluble hormones.
A
Hormones that are stored in membrane-bound secretory vesicles, circulate unbound in blood, and have a rapid onset with short duration
5
Q
Define lipid-soluble hormones.
A
Hormones that are often not stored, released due to lipid solubility, transported bound to carrier proteins, and have a slow onset with long duration
6
Q
What are the three main types of membrane receptors?
A
- Ion channel-linked receptors
- G-protein-coupled receptors
- Enzyme-linked receptors
7
Q
What is the role of the hormone-receptor complex in genomic effects?
A
It translocates to the nucleus and acts as a transcription factor to regulate gene transcription
8
Q
True or False: Water-soluble hormones primarily activate intracellular receptors.
A
False
9
Q
What is down-regulation in hormone signaling?
A
A decrease in receptor number and sensitivity due to prolonged activation by hormones
10
Q
Identify two determinants of hormone signal transduction sensitivity.
A
- Binding affinity of the receptor to the hormone
- Number of receptors on the target cell
11
Q
What are spare receptors?
A
Receptors in excess of the number required to produce a maximal biological response
12
Q
Fill in the blank: The hormone signaling cascade can amplify the signal by _______.
A
[producing a large cellular response]
13
Q
What is the difference between negative feedback and positive feedback mechanisms?
A
Negative feedback inhibits the original effect of the hormone, while positive feedback enhances it
14
Q
What is the potential consequence of obesity on insulin signaling?
A
Increased insulin levels leading to down-regulation of the receptor and insulin resistance
15
Q
What happens during the amplification of hormone signaling?
A
A few molecules of the hormone can produce a greatly amplified signal, triggering a large cellular response
16
Q
What is the term for the physiological response when hormone levels decrease, leading to increased sensitivity?
A
Up-regulation
17
Q
What are two examples of positive feedback mechanisms?
A
- Oxytocin release during labor
- Platelet aggregation at a damaged vessel site
18
Q
How do lipid-soluble hormones exert their effects?
A
By activating intracellular receptors that primarily employ nuclear pathways
19
Q
What is the primary mechanism of termination for signal transduction?
A
Receptor-mediated endocytosis and other enzymatic activities that decrease signaling
20
Q
What can excessive hormone levels lead to in terms of receptor activation?
A
Activation of similar receptors (spillover) and potential unintended biological responses
21
Q
What is the significance of receptor binding affinity in hormone signaling?
A
High affinity leads to prolonged activation of the receptor and hormone action
22
Q
Name a hormone that can activate both its own receptors and insulin-like growth factor-1 receptors.
A
Insulin
23
Q
What is the effect of exercise or caloric restriction on insulin sensitivity?
A
It reduces insulin levels, leading to up-regulation of insulin receptors and increased sensitivity
24
Q
Fill in the blank: Hormones have _______ receptors that make target cells more sensitive to low hormone levels.
A
[spare]
25
What is the primary function of eicosanoids as hormones?
They are fatty acid derivatives that act as signaling molecules in various physiological processes.
26
What is the role of ion channel-linked receptors?
Acts as gates in the cell membrane. Ligand binding opens the gate, allowing specific ions to pass through a channel in the receptor.
27
Name two types of calcium channels associated with ion channel-linked receptors.
* IP3 receptor (ER; Ca+2 channel)
* Ryanodine receptor (ER; Ca+2 channel)
28
What is the function of the nicotinic acetylcholine (nACh) receptor?
Increases Na+ and K+ permeability causing depolarization, leading to action potential and muscular contraction.
29
True or False: Muscarinic ACh receptors are ion-channel-coupled receptors.
False.
30
What is the largest family of cell membrane receptors?
G protein-coupled receptors (GPCR) with >1000 members.
31
What are the three subunits of a G protein?
* α
* β
* γ
32
How do GPCRs activate G proteins?
The GPCR induces the exchange of GDP for GTP, activating Gα.
33
What are the second messengers produced by GPCR activation?
* Cyclic AMP (cAMP)
* Inositol trisphosphate (IP3)
* Diacylglycerol (DAG)
34
What is the role of cAMP in cellular signaling?
Activates protein kinase A (PKA), which phosphorylates proteins or stimulates gene expression.
35
Fill in the blank: G proteins that stimulate adenylyl cyclase are known as G_____.
Gαs
36
How do enzyme-linked receptors differ from GPCRs?
Enzyme-linked receptors have intrinsic enzyme activity activated upon ligand binding, while GPCRs couple to G proteins.
37
What is the function of receptor guanylyl cyclases?
Convert GTP to cGMP in response to ligands like ANP and nitric oxide.
38
What is the FDA-approved drug that targets neprilysin?
Entresto (LCZ696)
39
What role do receptor tyrosine kinases (RTKs) play in cell signaling?
RTKs act as receptors with intrinsic tyrosine kinase activities, activating multiple signaling pathways.
40
Name an important pathway activated by RTKs.
PI-3-kinase-Akt-mTOR pathway.
41
What is the significance of Ras in cell signaling?
Regulates organ development, growth, and cell proliferation; mutated in 30% of human cancers.
42
What is the role of Akt in cell survival?
Phosphorylates and inactivates pro-apoptotic protein Bad, promoting cell survival.
43
True or False: Insulin receptor is a type of receptor tyrosine kinase.
True.
44
What is the effect of insulin on receptor substrates?
Phosphorylates insulin receptor substrate (IRS) at tyrosine residues, activating signaling cascades.
45
Fill in the blank: The activation of IRS leads to the activation of the PI-3-kinase-Akt signaling cascade, which regulates numerous enzymes and transcription factors that mediate the metabolic actions of _______.
insulin
46
What is the primary role of the MAP kinase pathway in relation to insulin?
Mediates the growth effects of insulin
## Footnote
The MAP kinase pathway is crucial for cellular growth and proliferation in response to insulin signaling.
47
Which serine residues are involved in the phosphorylation of IRS1-4 leading to insulin resistance?
mTOR/S6K, IKK, JNK, ERK, p38
## Footnote
These kinases contribute to the degradation of IRS, a major mechanism of insulin resistance.
48
What type of receptor is activated by an agonist to open an ion channel?
Ion channel-linked receptor
## Footnote
Examples include nicotinic Ach, IP3 receptor, and Ryanodine receptor.
49
What does a GPCR do upon activation?
Promotes GTP binding to a specific G protein
## Footnote
This leads to the activation of a specific pathway and the production of second messengers.
50
Which second messenger is produced by Gq activation?
IP3, DAG, and Ca++
## Footnote
Gq activates Phospholipase C, leading to the production of these second messengers.
51
What do ANP and NO activate to produce cGMP?
Membrane-bound guanylyl cyclase and soluble guanylyl cyclase
## Footnote
This process results in vasodilation.
52
What are the pathways activated by insulin, IGF-1, PDGF, FDF, and EGF?
Receptor tyrosine kinases leading to Ras, MAP kinase, and PI-3-Kinase-Akt-mTOR pathways
## Footnote
These pathways are essential for cellular signaling in response to these growth factors.
53
True or False: Heterotrimeric G proteins and small G proteins such as Ras have no similarities.
False
## Footnote
There are both similarities and differences between these two types of G proteins.
54
Fill in the blank: Insulin binds to an insulin receptor of an adipocyte, which leads to _______.
Tyrosine phosphorylation of IRS1-4
## Footnote
This is a key signaling process that occurs in response to insulin binding.
55
What is one of the signaling processes that occurs when insulin binds to its receptor?
Activation of protein kinase C to phosphorylate substrates
## Footnote
This is one of the options in the signaling cascade initiated by insulin.
56
adipose tissues secrete what hormone?
leptin
57
The intestines secrete incretins; what is an important one.
GLP-1/2
58
T or F: eicosanoids are fatty acid derivative hormones?
True
59
Describe how intracrine signaling works.
hormone is not released into the ECM and stays in the cytoplasm
many sex hormones use this kind of signaling
60
T or F: osteoclasts express RANK receptors on their cell surface and differentiate into osteoblasts when stimulated by PTH.
FALSE!!!
It is the other way around:
osteoblasts express PTH sensitive RANK receptors on their cell surface; when PTH binds to this receptor this results in a confrontational change to RANKL (activated form); osteoclast precursors can this bind to RANKL to stimulate further differentiation
61
80% of cancer pts. w/ hypercalcemia have elevated PTHrP. What is the physiological consequence of this?
Increases the rate of osteoclast formation which stimulate osteolysis and bone resorption
62
what do non-nuclear pathways regulate?
cytoplasmic and other cellular processes
63
T or F: steroid hormones do not produce rapid cellular effects independently of gene transcription.
FALSE
In fact, non-genomic effects of steroid hormones accounts for 5% of the total receptor sites
Researchers believe the non-genomic effects of steroid hormones are vital for their proper function
64
Where are receptors that induce non-genomic effects of steroid hormones located in the cell
localized to membrane caveolae
65
What are important hydrophobic hormones you need to know?
Steroids
Vit. D.
T3
T4
Retinoids
NO
66
T or F: eicosanoids are lipid soluble.
False
They are water soluble hormones
67
T or F: the same hormone can have vastly different effects in different tissue
THIS IS VERY MUCH TRUE
68
What determines sensitivity of hormone signal transduction?
# receptors on/in target cell
binding affinity
number of receptors on/in the target cell
69
What is the physiological effect for hormonal receptors w/ very high sensitivity for their corresponding hormone
high sensitivity = high affinity (low Kd); Hence, the substrate stays bound to its target receptor for a longer period ot time; the subsequent effect is prolonged activation of the receptor and therefore action of the hormone
70
T or F: NT receptors have low sensitivity/low affinity but very high specificity
True
71
what is the physiological effect of receptors w/ low sensitivity for their corresponding hormone
b/c of the higher Kd/affiniy, the hormones do not stay bound to their target receptors for long; this induces very rapid/instantaneous cellular response w/ a faster off-rate
72
T or F: all hormonal receptors much be substrate-occupied to induce a maximal biologic response
FALSE
hormones have spare receptors
73
what are the physiological consequences of hormones having a larger number of spare target receptors
increases receptor sensitivity to lower concentrations of hormone
When the hormonal concentration exceeds the required level to achieve maximal biologic effect, spare receptors are used to activate other biochemical processes; this can alter the cellular response and effect of the hormone
74
High levels of insulin activates which receptor and what is the consequential effect of this interaction?
At high levels, insulin activates IGF-1 receptors in the absence of GH; in other words, the cells alter their response to insulin as if it were a growth factor making insulin a pseudo growth factor
75
How does the cell respond to target receptors activated for prolonged periods of time
the cell reduces number of receptors; this lowers sensitivity in which case higher levels of hormone are needed to induce a normal physiological function
76
Adaptation/Desensitization/tolerance is an example of what?
negative feedback control
77
Serine kinases inactivate insulin as a means for negative feedback. T or F.
True
78
How does exercise reduce insulin levels?
During exercise, glucose quickly gets depleted; this up-regulates insulin receptors and its downstream signaling on GLUT4 transmembrane receptors
79
describe the feedback inhibition mechanism for glucocorticoids
high levels of glucocorticoids down-regulates production of ACTH from the anterior pituitary and CRH from the hypothalamus simultaneously
80
what is the physiological consequence of prolonged exposure to high levels of glucocorticoids
leads to adrenal gland atrophy which can cause adrenal insufficiency
81
Why does sudden discontinuation of a glucocorticoid cause adrenal insufficiency?
This is due to the negative feedback response in the HPA axis; when glucocorticoids are high, the expression of ACTH receptors in the adrenal glands decreases; so if the corticosteroid is abruptly withdrawn, the adrenal glands do not have enough ACTH receptors to produce sufficient amounts of cortisol
82
what are some examples of biological processes that work through ion channel-linked receptors
IP3 & CC receptors in the jER stimulate somatic muscle contraction
Ryanodine receptors in the ER
NICOTINIC Acetylcholine receptors: conduction signals mediated by Na & K
83
The pathophysiology of Myasthenia gravis involves autoantibodies directed against nACh receptors located at presynaptic NMJs
True
84
T or F: photons stimulate GPCRs on the cell surface of specialized cells in the retina to induce signal transduction of visual processes
True
85
What hormones act on Go GPCRs
arachidonic acid and eicosanoids
86
what hormones act on Gs GPCRs
epinephrine, ACTH, glucagon
87
what hormones act on Gq GPCRs
Angiotensin-II & endothelin-1
88
T or F: TSH acts on both Gq & Gs GPCRs
True
89
T or F: In humans, higher concentrations of TSH are required to activate Gs GPCRs
FALSE
higher concentrations are required to active the Gq inositol pathway
90
what kind of hormones target intracellular receptors
lipid soluble hormones
91
Both ANP & BNP are degraded by what protease
neutral endopeptidase: Neprilysin
92
natriuretic peptides target what type of receptor GC
GC-A
93
NO targes what type of receptor GC
sGC
94
cGMP activates what proteins in the cytoplasm
PKG & Phosphodiesterases
95
T or F: nitroglycerin inhibits NO-cGMP pathways
True
96
What GC pathways does Sildenafil/Viagra inhibit?
activation of PDE5
97
Vericiguat targets and stimulates what type of receptors?
sGC
98
what is the role of cytoplasmic PDE5
degrades cGMP as a negative feedback response
99
T or F: Ras proteins are a family of small monomeric G proteins.
True
100
What are some key differences b/t large and small G proteins
Small G proteins:
have an innate GTPase activity allowing them to auto inactivate themselves
act as intermediaries and more distal parts of the cascade
101
Ras activates what protein
MAP
102
T or F: Ras proteins are stimulated by RTKs
True
103
Most RTKs involved in cell growth active what protein
PI-3 kinase
104
PI-3 kinases can utilize what second-messenger involved in the Gq pathway to induce other cellular effects
IP3 or inositol phospholipids
105
what is the primary role of inositol phospholipids in the PI-3-kinase pathway
serves as a dock for activation of Akt/PKB
106
Describe hoe PKB promotes cell survival
inactivates pro-apoptotic protein Bad
activates mTOR, a serine/threonine kinase critical for cell growth
107
T or F: insulin targets RTKs that activate the PI-3 kinase/PKB pathway
True
108
what subunit of RTKs does insulin act on to elicit its cellular effects>
IRS at tyrosine and/or serine residues
109
Describe how insulin mediates growth effects
recruits a special protein complex that activates the MAP kinase pathway
110
EGFR is an RTK that is hyperstimulated for what disease
CANCERS
111
What are the characteristics of 'Traditional' hormones?
Secreted by a gland, integral for maintenance of homeostasis, physiologic function within pathologic states, secreted directly into blood, act on distant organs, secreted in small amounts.
112
What defines 'Non-Traditional' hormones?
Secreted by non-glandular organs, integral for maintenance of homeostasis, physiologic function within pathologic states, secreted directly into blood, act on distant organs, secreted in small amounts.
113
What is the definition of Endocrine?
Product of an organ circulating in the body and producing an effect remote from its point of origin.
114
What is the definition of Paracrine?
Product secreted by a cell and acting on adjacent cells.
115
What is the definition of Autocrine?
Product secreted by a cell and acting on the same cell.
116
What were Courtney Finnegan's vital signs upon presentation?
Pulse: 155 bpm, irregular; BP: 115/76 mmHg.
117
What were the laboratory diagnostics results for Courtney Finnegan?
Total CK: 144 IU/L; CK-MB: 2 IU/L; Troponin-I: 0.02 ng/mL; BNP: 540 pg/mL.
118
What is Heart Failure with reduced Ejection Fraction (HFrEF)?
Heart Failure with reduced Ejection Fraction (< 49%).
119
What is Heart Failure with preserved Ejection Fraction (HFpEF)?
Heart Failure with preserved Ejection Fraction (50-70%).
120
What are the three types of heart failure based on systolic and diastolic function?
* Left-Side Failure * Right-Side Failure * Diastolic Failure.
121
What are the types of endogenous natriuretic peptides?
* A-type Natriuretic peptide (ANP) * B-type Natriuretic peptide (BNP) * C-type Natriuretic peptide (CNP) * Urodilatin * Osteocrin * Musculin.
122
What is the primary stimulus for the release of A-type Natriuretic Peptide (ANP)?
Atrial wall stretch.
123
What are the normal plasma levels of Urodilatin?
Approximately 10 fmol/ml (20 pg/ml).
124
What is the role of Neprilysin?
Membrane-bound enzyme that degrades many peptide hormones with a higher affinity for ANP and CNP.
125
What is the effect of Natriuretic Peptides on blood pressure?
↓ Blood pressure.
126
What are the metabolic effects of Natriuretic Peptides?
* Regulation of satiety * ↑ Insulin secretion * ↑ Mitochondria number * ↑ Thermogenic energy use * ↓ Oxidative stress * ↓ Inflammation.
127
What are the clinical outcomes associated with BNP plasma concentration?
* < 100 pg/ml: UNLIKELY * 100 – 400 pg/ml: +/- * > 400 pg/ml: LIKELY.
128
What is the half-life of BNP in plasma?
4-20 minutes.
129
True or False: BNP is secreted by the heart and circulates in plasma.
True.
130
Fill in the blank: The FDA approved Nesiritide in ______.
2001.
131
What are the four distinct plasma membrane binding sites for Natriuretic Peptide Receptors (NPR)?
* NPR-A * NPR-B * NPR-C.
132
How many hormones have been identified in the gastrointestinal system?
Over two dozen hormones
## Footnote
Most of these hormones are peptides.
133
What are the two primary functions of gastrointestinal hormones?
Paracrine & endocrine function
134
Which hormone is secreted by G-cells?
Gastrin
135
What is the cell source of Histamine?
ECL cells
136
Which hormones are secreted by L-cells?
* Peptide YY
* GLP-1
137
What is the primary function of Cholecystokinin?
Regulation of digestion
138
What is the primary role of GLP-1?
Regulation of insulin release
139
Fill in the blank: Intestinal-derived proteins that increase glucose-stimulated insulin secretion are called _______.
Incretins
140
What major role does GIP play in the body?
Stimulates insulin release
141
What was significant about the year 1929 in relation to incretins?
Description of hypoglycemic effect of a duodeno-jejunal extract
142
What peptide was identified in porcine ileal mucosa in 1987?
Insulinotropic peptide
143
What is the parent molecule from which glucagon-like peptides (GLP-1, GLP-2) are derived?
Proglucagon
144
What is the action of Dipeptidyl peptidase-4 (DPP4) on GLP-1?
Degrades GLP-1
145
True or False: GLP-1R is a seven-transmembrane G-protein-coupled receptor.
True
146
What physiological effect does GLP-1 have on inflammation?
↓ Inflammation
147
List three organs where GLP-1R is expressed.
* Liver
* Kidney
* Pancreatic islets
148
What is one of the effects of GLP-1 on appetite?
↓ Appetite
149
Which pathway is activated by GLP-1R that contributes to its physiological effects?
cAMP-PKA pathway
150
What effect does GLP-1 have on gastric emptying?
↓ Gastric emptying
151
Fill in the blank: GLP-1 increases _______ uptake.
Glucose
152
What is the normal range for Erythropoietin levels?
0.0 - 27 units/L
153
What is the hematocrit percentage that indicates anemia?
24.2%
154
What is the significance of a high Erythropoietin level in the context of anemia?
Indicates increased production in response to low oxygen levels
155
What is the normal range for Hemoglobin (HGB)?
12.0 - 16.0 g/dL
156
What is the MCV value that indicates microcytic anemia?
56.8 fL
157
What hormone is synthesized and stored by Juxtaglomerular (JG) cells in the kidney?
RENIN
## Footnote
Renin is the rate-limiting enzyme of the Renin-Angiotensin-Aldosterone System (RAAS).
158
Where is CALCITRIOL synthesized in the kidney?
Proximal tubules
## Footnote
Calcitriol is synthesized from 25-OH Vitamin D (calcifediol) via the enzyme 1-α-hydroxylase (CYP27B1).
159
What is the primary function of Erythropoietin (EPO)?
Regulates proliferation and maturation of erythroid progenitors
## Footnote
EPO is crucial for red blood cell production.
160
In which year was it discovered that decreased pO2 is associated with erythropoiesis?
1893
161
What is the main site of EPO production in adults?
Renal Epo-Producing cells (REPs) in the corticomedullary border
## Footnote
Approximately 80-85% of EPO is produced in this area.
162
What is the role of EPO in response to hypoxia?
Stimulates EPO production
## Footnote
EPO is produced when a person is exposed to low oxygen levels.
163
What does HIF stand for in the context of EPO production regulation?
Hypoxia-Inducible Factor
164
What is the significance of the α subunit of HIF?
It has 3 isoforms (1α-3α) and plays a key role in the response to hypoxia
165
What are the two types of receptors for Erythropoietin?
HETERODIMERIC and MONODIMERIC
## Footnote
HETERODIMERIC receptors are found in brain, kidney, myocardial, and endothelial cells, while MONODIMERIC receptors are located on erythroid progenitor cell membranes.
166
What is the effect of EPO binding to its receptor?
Activates JAK2/STAT5, PI3K, and MAPK pathways
## Footnote
This leads to survival, proliferation, and maturation of erythroid cells.
167
Fill in the blank: EPO is a _______ that is crucial for the production of red blood cells.
glycoprotein
168
What is the clinical significance of dysregulation of EPO in serum?
Anemia, Polycythemia, Renal cancer, Renal failure
169
What percentage of renal blood flow (RBF) is supplied by the kidneys?
20%-25% of cardiac output (CO)
170
What does the term 'normoxia' refer to in relation to EPO synthesis?
Normal oxygen levels
171
What is the primary role of prolyl hydroxylase domain (PHD) enzymes?
Regulate HIF activity in an O2-dependent manner
172
What are the erythroid precursors involved in EPO signaling?
BFU-E, CFU-E, ProE, BasoE, PolyE, OrthoE, Retic
## Footnote
BFU-E: Burst-forming unit-erythroid, CFU-E: Colony-forming unit-erythroid, ProE: Proerythroblast, BasoE: Basophilic erythroblast, PolyE: Polychromatic erythroblast, OrthoE: Orthochromatic erythroblast, Retic: Reticulocyte.
173
What are the conditions associated with EPO levels in health and disease?
Normal, Anemias, Uremia, 2° Erythrocytosis, 1° Erythrocytosis
## Footnote
Uremia is a complication of chronic kidney disease and acute kidney injury.
174
T or F: right-side diastolic heart failure does not exist.
True
175
T or F: Right-side heart failure can happen independently of left-side function.
False: systolic failure is always assoc. w/ left-sided heart failure
176
How is diastolic left-side heart failure quantitatively defined
preserved ejection fraction (50-70%)
177
How is systolic left-side heart failure quantitatively defined
reduced ejection fraction (<49%)
178
T or F: Plasma levels of ANP correlate w/ severity of symptomatic HF?
True
179
T or F: ANP is secreted directly into the blood stream right after synthesis.
False
ANP is stored within granules of atrial cells and get released by external stimuli
180
what are primary stimuli for ANP relase?
Atrial wall stretch
181
what are secondary stimuli for ANP relase?
endothelin, Angiotensin II, AVP
182
what are primary stimuli for BNP relase?
wall stretch and increased transmural ventricular pressure
183
High concentrations of BNP in cardiac ventricles and circulation can indicate what cardiopathies
Ventricular HF
post-MI event
184
Endothelial shear stress stimulates the release of what natriuretic peptides from vascular endothelium
CNP
185
Describe the various pathways by which natriuretic peptide receptors are degraded?
Gi, Gq, neutral endopeptidases (Neprilysin)
186
T or F: NPR-A has equal affinity for both ANP & BNP.
True
187
NPR-B is specific for which NP
CNP
188
What incretin stimulates the feeling of satiety
GLPs
189
what incretin is involved in the facilitation of triglyceride storage
GIP
190
Prohormone convertase generates what?
alpha-cells
glucagon
GRPP
GLP 1 & 2
Glicentin
oxyntomodulin
191
T or F: GLP receptors are Gs
True
192
what incretin promotes beta-cell proliferation
GLP-1
193
GLP-1Rs are densely expressed in what CNS tract?
Nucleus Tractus Solitarii
194
GLP-1Rs are densely expressed in what nucelus?
paraventricular nucleus
195
what role does calcitriol play int the endocrine kindy
vitamin D synthesis precursor
196
T or F: during fetal development, EPO is primarily produced in the kidneys
False
mostly produced in hepatocytes
197
During normoxia, EPO synthesis only occurs in what zone of the kindeys
inner cortex
198
HIF-1alpha secretion is stimulated by low O2 levels and becomes the target of what enzyme
PHD
199
Using your knowledge of Hemoglobin synthesis, what other proteins can you guess are upregulated in the presence of active PHD besides EPO
ferroportin
transferrin
VEGF-A
200
What is the cellular response to EPO?
survival
proliferation
maturation
201
Monomeric EPO receptors are only expressed on reticulocytes. T or F?
FALSE
they are only expressed on the cell membranes of erythroid progenitor cells
202
What other incretin in conjunction w/ GLP also helps to stimulate satiety
oxyntomodulin
203
What are the different types of adipose tissue?
* Visceral (Intrabdominal)
* Subcutaneous
* Dermal
* Femoral
* Gluteal
* Abdominal
* Upper
* Cranial
* Gonadal
* Perirenal
* Omental
* Mesenteric
* Retroperitoneal
* Epicardial
## Footnote
These depots exhibit distinct metabolic profiles and health implications.
204
What is the relationship between upper body fat deposition and metabolic dysfunction?
Fat deposition in the upper body is linked to a higher risk of metabolic dysfunction
## Footnote
This includes visceral and subcutaneous abdominal fat.
205
How does lower body adiposity relate to metabolic risk?
Lower body adiposity is associated with lower risk and may be protective
## Footnote
This includes subcutaneous, gluteal, and femoral fat.
206
What are the constituents of adipose tissue aside from adipocytes?
* Endothelial cells
* Fibroblasts
* Pericytes
* Pre-adipocytes
* Macrophages (pro- and anti-inflammatory)
* Immune cells (T-cells, B-cells, PMNs)
## Footnote
Together, these are referred to as the adipose tissue stromal vascular fraction (SVF).
207
What is the role of the adipose tissue stromal vascular fraction (SVF)?
SVF produces hormones and cytokines that can act in a paracrine manner
## Footnote
Alterations in SVF due to metabolic diseases is an area of active investigation.
208
True or False: Women have a higher cardiometabolic risk associated with fat distribution than men.
False
## Footnote
Fat distribution in women is associated with lower cardiometabolic risk.
209
What is the significance of gluteal and femoral depots in women?
These depots are more insulin-sensitive compared to visceral adipose tissue
## Footnote
They secrete more metabolically favorable adipokines such as adiponectin.
210
What are homeobox genes?
Homeobox genes code for protein transcription factors
## Footnote
They exhibit expression patterns in fat depots due to differences in gene homeodomains.
211
What are the different types of adipocytes based on color?
* White adipose tissue (WAT)
* Brown adipose tissue (BAT)
* Beige adipose tissue
## Footnote
These types differ in their shape, size, and function.
212
What is the primary function of white adipose tissue (WAT)?
Critical for energy storage, endocrine communication, and insulin sensitivity
## Footnote
WAT comprises the largest volume of adipose tissue.
213
Where is brown adipose tissue (BAT) primarily located in adults?
In the supraclavicular and thoracic regions
## Footnote
BAT is metabolically active and contributes to whole-body fat oxidation.
214
What induces the 'beiging' of white adipose tissue?
* Diet
* Exercise
* Pre- and post-biotics
* Pharmaceutical agents
* Numerous plant-based bioactive compounds
* Adipokines
## Footnote
Beiging may protect against obesity and associated metabolic dysfunction.
215
What are uncoupling proteins (UCPs)?
Members of the mitochondrial anion carrier family that convert mitochondrial proton-motive force into heat
## Footnote
UCP1 is involved in adaptive thermogenesis.
216
What triggers lipolysis in adipose tissue?
Mobilization of TAG when metabolic fuels are low and/or energy demand is high
## Footnote
This process is regulated by hormones and the sympathetic nervous system.
217
What is leptin and its primary function?
A 16 kDa peptide hormone that regulates food intake (satiety)
## Footnote
It is primarily expressed in white adipose tissue.
218
What are the forms of adiponectin?
* Monomeric form
* Globular form
* Trimeric form
* Hexameric form
* Multimeric form
## Footnote
MMW and HMW oligomers make up most of the circulating adiponectin.
219
What is the role of adiponectin in the body?
Increases insulin sensitivity and has anti-inflammatory effects
## Footnote
It inhibits liver fibrosis and is increased by thiazolidinediones.
220
What receptors are involved in adiponectin signaling?
* AdipoR1
* AdipoR2
* T-cadherin
## Footnote
They modulate insulin sensitivity and metabolic gene expression.
221
What is the primary function of AdipoR2?
Modulates insulin sensitivity and metabolic gene expression in insulin-responsive tissues
## Footnote
AdipoR2 is involved in the activation of AMP-dependent protein kinase (AMPK), which promotes fatty acid oxidation.
222
Which tissues express AdipoR2?
Skeletal muscle, liver
## Footnote
These tissues are critical for insulin responsiveness and metabolic regulation.
223
What does T-cadherin activate?
PPARα via unidentified pathways
## Footnote
T-cadherin is found in cardiac myocytes, vascular endothelial cells, and smooth muscle cells.
224
What is the primary effector of cardioprotection by adiponectin?
T-cadherin
## Footnote
Adiponectin is known for its protective effects on the heart, mediated through T-cadherin.
225
What are small molecule activators of adiponectin signaling promising for?
Management of insulin resistance, NAFLD & T2D
## Footnote
These conditions are linked to metabolic dysregulation.
226
Which pathways are involved in increasing glucose metabolism, fatty acid oxidation, and insulin sensitivity?
PPAR-α, AMPK, Ca++, CAMKK, PKC
## Footnote
These pathways play a significant role in metabolic regulation.
227
What are the different forms of adiponectin mentioned?
* LMW adiponectin
* Globular adiponectin
* HMW adiponectin
## Footnote
Each form may have distinct biological activities and effects.
228
What is resistin and where is it predominantly secreted from?
A major adipose tissue-derived hormone, predominantly secreted from macrophages
## Footnote
Resistin is involved in inflammation and metabolic processes.
229
What is the molecular weight of resistin?
Approximately 12.5 kDa
## Footnote
This size classifies it as a small protein.
230
What are the effects of resistin?
* Induces low-grade inflammation by stimulating monocytes
* Induces insulin resistance
* Inhibits differentiation of adipocytes in vitro
## Footnote
These effects contribute to metabolic dysfunction.
231
Where are distinct patterns of resistin expression found?
* Inguinal
* Gonadal
* Retroperitoneal
* Mesenteric (WAT depots)
* BAT
## Footnote
Each type of adipose tissue exhibits unique expression patterns.
232
What inhibits the expression of resistin?
Thiazolidinediones (TZDs)
## Footnote
TZDs are a class of medications used to treat insulin resistance.
233
Which two known receptors does resistin interact with?
* Toll-like receptor 4 (TLR4)
* Adenylyl cyclase-associated protein 1 (CAP1)
## Footnote
These interactions are crucial for resistin's proinflammatory effects.
234
True or False: Epidemiological, genetic, and clinical data support a role for resistin in dysfunctional metabolism and related pathologies.
True
## Footnote
This evidence highlights resistin's potential impact on metabolic health.
235
What is the therapeutic value of interventions to antagonize resistin action?
Remains undetermined in the treatment of metabolic or cardiovascular disease in humans
## Footnote
Further research is needed to clarify its therapeutic implications.
236
what kind of cell signaling do adipocytes use?
paracrine
237
what AT receptors are ubiquitously expressed in all fat types and storage regions
B1 & 2
238
What ATRs are only expressed in white AT?
B3
239
AT in what regions of the body is densely expressed w/ A2 receptors
subcutaneous human AT
240
What is the cellular effect of B3
stimulation of lipolysis
241
what is the cellular effect of A2
inhibits lipolysis
242
White APCs express what receptor on their surfaces
PPARgamma
243
Brown APCs express what receptor on their surface
Myf5+
244
Myf5- APCs differentiates in to what type of adipocytes
beige
245
T or F: Adipose Tissue is derived from the endodermin
False
adipocytes have mesodermal origin
246
T or F: adipocytes are derived from the myeloid linage of cells
True
247
BMD-APCs are expressed in higher numbers for obese pts. What is the clinical significance of this?
BMD-APCs reduce expression of genes involved in lipid metabolism
they also increases gene expression of pro-inflammatory agents
248
what are pink adipocytes and what is their function
high expression during pregnancy and throughout lactation
form milk-secreting alveoli
structure is more epithelia in nature
249
T or F: White AT has the highest thermogenesis capability
FALSE
Brown AT has the greatest capacity for thermogenesis
seems to be correlated w/ # of mitochondria
250
T or F: WAT has the greatest capacity to store lipids
True
251
what type of APC expressess high levels of UCP1/thermogenin
BATs
252
UCP3 is highly expressed in what tissue
skeletal muscle
253
UCP4 & 5 are expressed where
CNS
254
what conditions promote de novo lipogenesis
caloric restriction
adaptive thermogenesis
255
how does insulin supress lipolysis
increasses activity of PDE3 and decreasing cAMP levels
256
T or F: exercise is the major pro-lipolytic stimulus in humans.
THIS IS VERY TRUE AND THE MOST EFFEECTIVE WAY TO DECREASE BMI
257
leptin is dysregulated in what malignancies
breast, endometrial, thyroid, GI
258
T or F: leptin is underexpressed in break cancer ,malignancies
ture
