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Endocrinology > Endocrine Physiology > Flashcards

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

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2
Q

List the classic endocrine glands.

A
  • Heart
  • Kidney
  • Adipose tissue
  • Stomach
  • Intestines
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3
Q

What are the chemical structures of hormones?

A
  • Protein or Peptide
  • Amino acid derivatives (amines)
  • Steroids
  • Fatty acid derivatives
  • Gases
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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

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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

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6
Q

What are the three main types of membrane receptors?

A
  • Ion channel-linked receptors
  • G-protein-coupled receptors
  • Enzyme-linked receptors
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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

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8
Q

True or False: Water-soluble hormones primarily activate intracellular receptors.

A

False

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9
Q

What is down-regulation in hormone signaling?

A

A decrease in receptor number and sensitivity due to prolonged activation by hormones

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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
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11
Q

What are spare receptors?

A

Receptors in excess of the number required to produce a maximal biological response

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12
Q

Fill in the blank: The hormone signaling cascade can amplify the signal by _______.

A

[producing a large cellular response]

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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

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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

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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

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16
Q

What is the term for the physiological response when hormone levels decrease, leading to increased sensitivity?

A

Up-regulation

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17
Q

What are two examples of positive feedback mechanisms?

A
  • Oxytocin release during labor
  • Platelet aggregation at a damaged vessel site
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18
Q

How do lipid-soluble hormones exert their effects?

A

By activating intracellular receptors that primarily employ nuclear pathways

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19
Q

What is the primary mechanism of termination for signal transduction?

A

Receptor-mediated endocytosis and other enzymatic activities that decrease signaling

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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

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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

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22
Q

Name a hormone that can activate both its own receptors and insulin-like growth factor-1 receptors.

A

Insulin

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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

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24
Q

Fill in the blank: Hormones have _______ receptors that make target cells more sensitive to low hormone levels.

A

[spare]

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25
Q

What is the primary function of eicosanoids as hormones?

A

They are fatty acid derivatives that act as signaling molecules in various physiological processes.

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26
Q

What is the role of ion channel-linked receptors?

A

Acts as gates in the cell membrane. Ligand binding opens the gate, allowing specific ions to pass through a channel in the receptor.

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27
Q

Name two types of calcium channels associated with ion channel-linked receptors.

A
  • IP3 receptor (ER; Ca+2 channel)
  • Ryanodine receptor (ER; Ca+2 channel)
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28
Q

What is the function of the nicotinic acetylcholine (nACh) receptor?

A

Increases Na+ and K+ permeability causing depolarization, leading to action potential and muscular contraction.

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29
Q

True or False: Muscarinic ACh receptors are ion-channel-coupled receptors.

A

False.

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30
Q

What is the largest family of cell membrane receptors?

A

G protein-coupled receptors (GPCR) with >1000 members.

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31
Q

What are the three subunits of a G protein?

A
  • α
  • β
  • γ
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32
Q

How do GPCRs activate G proteins?

A

The GPCR induces the exchange of GDP for GTP, activating Gα.

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33
Q

What are the second messengers produced by GPCR activation?

A
  • Cyclic AMP (cAMP)
  • Inositol trisphosphate (IP3)
  • Diacylglycerol (DAG)
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34
Q

What is the role of cAMP in cellular signaling?

A

Activates protein kinase A (PKA), which phosphorylates proteins or stimulates gene expression.

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35
Q

Fill in the blank: G proteins that stimulate adenylyl cyclase are known as G_____.

A

Gαs

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36
Q

How do enzyme-linked receptors differ from GPCRs?

A

Enzyme-linked receptors have intrinsic enzyme activity activated upon ligand binding, while GPCRs couple to G proteins.

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37
Q

What is the function of receptor guanylyl cyclases?

A

Convert GTP to cGMP in response to ligands like ANP and nitric oxide.

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38
Q

What is the FDA-approved drug that targets neprilysin?

A

Entresto (LCZ696)

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39
Q

What role do receptor tyrosine kinases (RTKs) play in cell signaling?

A

RTKs act as receptors with intrinsic tyrosine kinase activities, activating multiple signaling pathways.

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40
Q

Name an important pathway activated by RTKs.

A

PI-3-kinase-Akt-mTOR pathway.

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41
Q

What is the significance of Ras in cell signaling?

A

Regulates organ development, growth, and cell proliferation; mutated in 30% of human cancers.

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42
Q

What is the role of Akt in cell survival?

A

Phosphorylates and inactivates pro-apoptotic protein Bad, promoting cell survival.

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43
Q

True or False: Insulin receptor is a type of receptor tyrosine kinase.

A

True.

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44
Q

What is the effect of insulin on receptor substrates?

A

Phosphorylates insulin receptor substrate (IRS) at tyrosine residues, activating signaling cascades.

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45
Q

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 _______.

A

insulin

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46
Q

What is the primary role of the MAP kinase pathway in relation to insulin?

A

Mediates the growth effects of insulin

The MAP kinase pathway is crucial for cellular growth and proliferation in response to insulin signaling.

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47
Q

Which serine residues are involved in the phosphorylation of IRS1-4 leading to insulin resistance?

A

mTOR/S6K, IKK, JNK, ERK, p38

These kinases contribute to the degradation of IRS, a major mechanism of insulin resistance.

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48
Q

What type of receptor is activated by an agonist to open an ion channel?

A

Ion channel-linked receptor

Examples include nicotinic Ach, IP3 receptor, and Ryanodine receptor.

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49
Q

What does a GPCR do upon activation?

A

Promotes GTP binding to a specific G protein

This leads to the activation of a specific pathway and the production of second messengers.

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50
Q

Which second messenger is produced by Gq activation?

A

IP3, DAG, and Ca++

Gq activates Phospholipase C, leading to the production of these second messengers.

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51
Q

What do ANP and NO activate to produce cGMP?

A

Membrane-bound guanylyl cyclase and soluble guanylyl cyclase

This process results in vasodilation.

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52
Q

What are the pathways activated by insulin, IGF-1, PDGF, FDF, and EGF?

A

Receptor tyrosine kinases leading to Ras, MAP kinase, and PI-3-Kinase-Akt-mTOR pathways

These pathways are essential for cellular signaling in response to these growth factors.

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53
Q

True or False: Heterotrimeric G proteins and small G proteins such as Ras have no similarities.

A

False

There are both similarities and differences between these two types of G proteins.

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54
Q

Fill in the blank: Insulin binds to an insulin receptor of an adipocyte, which leads to _______.

A

Tyrosine phosphorylation of IRS1-4

This is a key signaling process that occurs in response to insulin binding.

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55
Q

What is one of the signaling processes that occurs when insulin binds to its receptor?

A

Activation of protein kinase C to phosphorylate substrates

This is one of the options in the signaling cascade initiated by insulin.

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56
Q

adipose tissues secrete what hormone?

A

leptin

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57
Q

The intestines secrete incretins; what is an important one.

A

GLP-1/2

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58
Q

T or F: eicosanoids are fatty acid derivative hormones?

A

True

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59
Q

Describe how intracrine signaling works.

A

hormone is not released into the ECM and stays in the cytoplasm
many sex hormones use this kind of signaling

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60
Q

T or F: osteoclasts express RANK receptors on their cell surface and differentiate into osteoblasts when stimulated by PTH.

A

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

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61
Q

80% of cancer pts. w/ hypercalcemia have elevated PTHrP. What is the physiological consequence of this?

A

Increases the rate of osteoclast formation which stimulate osteolysis and bone resorption

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62
Q

what do non-nuclear pathways regulate?

A

cytoplasmic and other cellular processes

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63
Q

T or F: steroid hormones do not produce rapid cellular effects independently of gene transcription.

A

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

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64
Q

Where are receptors that induce non-genomic effects of steroid hormones located in the cell

A

localized to membrane caveolae

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65
Q

What are important hydrophobic hormones you need to know?

A

Steroids
Vit. D.
T3
T4
Retinoids
NO

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66
Q

T or F: eicosanoids are lipid soluble.

A

False
They are water soluble hormones

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67
Q

T or F: the same hormone can have vastly different effects in different tissue

A

THIS IS VERY MUCH TRUE

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68
Q

What determines sensitivity of hormone signal transduction?

A

receptors on/in target cell

binding affinity
number of receptors on/in the target cell

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69
Q

What is the physiological effect for hormonal receptors w/ very high sensitivity for their corresponding hormone

A

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

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70
Q

T or F: NT receptors have low sensitivity/low affinity but very high specificity

A

True

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71
Q

what is the physiological effect of receptors w/ low sensitivity for their corresponding hormone

A

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

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72
Q

T or F: all hormonal receptors much be substrate-occupied to induce a maximal biologic response

A

FALSE
hormones have spare receptors

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73
Q

what are the physiological consequences of hormones having a larger number of spare target receptors

A

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

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74
Q

High levels of insulin activates which receptor and what is the consequential effect of this interaction?

A

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

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75
Q

How does the cell respond to target receptors activated for prolonged periods of time

A

the cell reduces number of receptors; this lowers sensitivity in which case higher levels of hormone are needed to induce a normal physiological function

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76
Q

Adaptation/Desensitization/tolerance is an example of what?

A

negative feedback control

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77
Q

Serine kinases inactivate insulin as a means for negative feedback. T or F.

A

True

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78
Q

How does exercise reduce insulin levels?

A

During exercise, glucose quickly gets depleted; this up-regulates insulin receptors and its downstream signaling on GLUT4 transmembrane receptors

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79
Q

describe the feedback inhibition mechanism for glucocorticoids

A

high levels of glucocorticoids down-regulates production of ACTH from the anterior pituitary and CRH from the hypothalamus simultaneously

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80
Q

what is the physiological consequence of prolonged exposure to high levels of glucocorticoids

A

leads to adrenal gland atrophy which can cause adrenal insufficiency

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81
Q

Why does sudden discontinuation of a glucocorticoid cause adrenal insufficiency?

A

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

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82
Q

what are some examples of biological processes that work through ion channel-linked receptors

A

IP3 & CC receptors in the jER stimulate somatic muscle contraction
Ryanodine receptors in the ER
NICOTINIC Acetylcholine receptors: conduction signals mediated by Na & K

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83
Q

The pathophysiology of Myasthenia gravis involves autoantibodies directed against nACh receptors located at presynaptic NMJs

A

True

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84
Q

T or F: photons stimulate GPCRs on the cell surface of specialized cells in the retina to induce signal transduction of visual processes

A

True

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85
Q

What hormones act on Go GPCRs

A

arachidonic acid and eicosanoids

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86
Q

what hormones act on Gs GPCRs

A

epinephrine, ACTH, glucagon

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87
Q

what hormones act on Gq GPCRs

A

Angiotensin-II & endothelin-1

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88
Q

T or F: TSH acts on both Gq & Gs GPCRs

A

True

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89
Q

T or F: In humans, higher concentrations of TSH are required to activate Gs GPCRs

A

FALSE
higher concentrations are required to active the Gq inositol pathway

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90
Q

what kind of hormones target intracellular receptors

A

lipid soluble hormones

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91
Q

Both ANP & BNP are degraded by what protease

A

neutral endopeptidase: Neprilysin

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92
Q

natriuretic peptides target what type of receptor GC

A

GC-A

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93
Q

NO targes what type of receptor GC

A

sGC

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94
Q

cGMP activates what proteins in the cytoplasm

A

PKG & Phosphodiesterases

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95
Q

T or F: nitroglycerin inhibits NO-cGMP pathways

A

True

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96
Q

What GC pathways does Sildenafil/Viagra inhibit?

A

activation of PDE5

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97
Q

Vericiguat targets and stimulates what type of receptors?

A

sGC

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98
Q

what is the role of cytoplasmic PDE5

A

degrades cGMP as a negative feedback response

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99
Q

T or F: Ras proteins are a family of small monomeric G proteins.

A

True

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100
Q

What are some key differences b/t large and small G proteins

A

Small G proteins:
have an innate GTPase activity allowing them to auto inactivate themselves
act as intermediaries and more distal parts of the cascade

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101
Q

Ras activates what protein

A

MAP

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102
Q

T or F: Ras proteins are stimulated by RTKs

A

True

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103
Q

Most RTKs involved in cell growth active what protein

A

PI-3 kinase

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104
Q

PI-3 kinases can utilize what second-messenger involved in the Gq pathway to induce other cellular effects

A

IP3 or inositol phospholipids

105
Q

what is the primary role of inositol phospholipids in the PI-3-kinase pathway

A

serves as a dock for activation of Akt/PKB

106
Q

Describe hoe PKB promotes cell survival

A

inactivates pro-apoptotic protein Bad

activates mTOR, a serine/threonine kinase critical for cell growth

107
Q

T or F: insulin targets RTKs that activate the PI-3 kinase/PKB pathway

108
Q

what subunit of RTKs does insulin act on to elicit its cellular effects>

A

IRS at tyrosine and/or serine residues

109
Q

Describe how insulin mediates growth effects

A

recruits a special protein complex that activates the MAP kinase pathway

110
Q

EGFR is an RTK that is hyperstimulated for what disease

111
Q

What are the characteristics of ‘Traditional’ hormones?

A

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
Q

What defines ‘Non-Traditional’ hormones?

A

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
Q

What is the definition of Endocrine?

A

Product of an organ circulating in the body and producing an effect remote from its point of origin.

114
Q

What is the definition of Paracrine?

A

Product secreted by a cell and acting on adjacent cells.

115
Q

What is the definition of Autocrine?

A

Product secreted by a cell and acting on the same cell.

116
Q

What were Courtney Finnegan’s vital signs upon presentation?

A

Pulse: 155 bpm, irregular; BP: 115/76 mmHg.

117
Q

What were the laboratory diagnostics results for Courtney Finnegan?

A

Total CK: 144 IU/L; CK-MB: 2 IU/L; Troponin-I: 0.02 ng/mL; BNP: 540 pg/mL.

118
Q

What is Heart Failure with reduced Ejection Fraction (HFrEF)?

A

Heart Failure with reduced Ejection Fraction (< 49%).

119
Q

What is Heart Failure with preserved Ejection Fraction (HFpEF)?

A

Heart Failure with preserved Ejection Fraction (50-70%).

120
Q

What are the three types of heart failure based on systolic and diastolic function?

A
  • Left-Side Failure * Right-Side Failure * Diastolic Failure.
121
Q

What are the types of endogenous natriuretic peptides?

A
  • A-type Natriuretic peptide (ANP) * B-type Natriuretic peptide (BNP) * C-type Natriuretic peptide (CNP) * Urodilatin * Osteocrin * Musculin.
122
Q

What is the primary stimulus for the release of A-type Natriuretic Peptide (ANP)?

A

Atrial wall stretch.

123
Q

What are the normal plasma levels of Urodilatin?

A

Approximately 10 fmol/ml (20 pg/ml).

124
Q

What is the role of Neprilysin?

A

Membrane-bound enzyme that degrades many peptide hormones with a higher affinity for ANP and CNP.

125
Q

What is the effect of Natriuretic Peptides on blood pressure?

A

↓ Blood pressure.

126
Q

What are the metabolic effects of Natriuretic Peptides?

A
  • Regulation of satiety * ↑ Insulin secretion * ↑ Mitochondria number * ↑ Thermogenic energy use * ↓ Oxidative stress * ↓ Inflammation.
127
Q

What are the clinical outcomes associated with BNP plasma concentration?

A
  • < 100 pg/ml: UNLIKELY * 100 – 400 pg/ml: +/- * > 400 pg/ml: LIKELY.
128
Q

What is the half-life of BNP in plasma?

A

4-20 minutes.

129
Q

True or False: BNP is secreted by the heart and circulates in plasma.

130
Q

Fill in the blank: The FDA approved Nesiritide in ______.

131
Q

What are the four distinct plasma membrane binding sites for Natriuretic Peptide Receptors (NPR)?

A
  • NPR-A * NPR-B * NPR-C.
132
Q

How many hormones have been identified in the gastrointestinal system?

A

Over two dozen hormones

Most of these hormones are peptides.

133
Q

What are the two primary functions of gastrointestinal hormones?

A

Paracrine & endocrine function

134
Q

Which hormone is secreted by G-cells?

135
Q

What is the cell source of Histamine?

136
Q

Which hormones are secreted by L-cells?

A
  • Peptide YY
  • GLP-1
137
Q

What is the primary function of Cholecystokinin?

A

Regulation of digestion

138
Q

What is the primary role of GLP-1?

A

Regulation of insulin release

139
Q

Fill in the blank: Intestinal-derived proteins that increase glucose-stimulated insulin secretion are called _______.

140
Q

What major role does GIP play in the body?

A

Stimulates insulin release

141
Q

What was significant about the year 1929 in relation to incretins?

A

Description of hypoglycemic effect of a duodeno-jejunal extract

142
Q

What peptide was identified in porcine ileal mucosa in 1987?

A

Insulinotropic peptide

143
Q

What is the parent molecule from which glucagon-like peptides (GLP-1, GLP-2) are derived?

A

Proglucagon

144
Q

What is the action of Dipeptidyl peptidase-4 (DPP4) on GLP-1?

A

Degrades GLP-1

145
Q

True or False: GLP-1R is a seven-transmembrane G-protein-coupled receptor.

146
Q

What physiological effect does GLP-1 have on inflammation?

A

↓ Inflammation

147
Q

List three organs where GLP-1R is expressed.

A
  • Liver
  • Kidney
  • Pancreatic islets
148
Q

What is one of the effects of GLP-1 on appetite?

A

↓ Appetite

149
Q

Which pathway is activated by GLP-1R that contributes to its physiological effects?

A

cAMP-PKA pathway

150
Q

What effect does GLP-1 have on gastric emptying?

A

↓ Gastric emptying

151
Q

Fill in the blank: GLP-1 increases _______ uptake.

152
Q

What is the normal range for Erythropoietin levels?

A

0.0 - 27 units/L

153
Q

What is the hematocrit percentage that indicates anemia?

154
Q

What is the significance of a high Erythropoietin level in the context of anemia?

A

Indicates increased production in response to low oxygen levels

155
Q

What is the normal range for Hemoglobin (HGB)?

A

12.0 - 16.0 g/dL

156
Q

What is the MCV value that indicates microcytic anemia?

157
Q

What hormone is synthesized and stored by Juxtaglomerular (JG) cells in the kidney?

A

RENIN

Renin is the rate-limiting enzyme of the Renin-Angiotensin-Aldosterone System (RAAS).

158
Q

Where is CALCITRIOL synthesized in the kidney?

A

Proximal tubules

Calcitriol is synthesized from 25-OH Vitamin D (calcifediol) via the enzyme 1-α-hydroxylase (CYP27B1).

159
Q

What is the primary function of Erythropoietin (EPO)?

A

Regulates proliferation and maturation of erythroid progenitors

EPO is crucial for red blood cell production.

160
Q

In which year was it discovered that decreased pO2 is associated with erythropoiesis?

161
Q

What is the main site of EPO production in adults?

A

Renal Epo-Producing cells (REPs) in the corticomedullary border

Approximately 80-85% of EPO is produced in this area.

162
Q

What is the role of EPO in response to hypoxia?

A

Stimulates EPO production

EPO is produced when a person is exposed to low oxygen levels.

163
Q

What does HIF stand for in the context of EPO production regulation?

A

Hypoxia-Inducible Factor

164
Q

What is the significance of the α subunit of HIF?

A

It has 3 isoforms (1α-3α) and plays a key role in the response to hypoxia

165
Q

What are the two types of receptors for Erythropoietin?

A

HETERODIMERIC and MONODIMERIC

HETERODIMERIC receptors are found in brain, kidney, myocardial, and endothelial cells, while MONODIMERIC receptors are located on erythroid progenitor cell membranes.

166
Q

What is the effect of EPO binding to its receptor?

A

Activates JAK2/STAT5, PI3K, and MAPK pathways

This leads to survival, proliferation, and maturation of erythroid cells.

167
Q

Fill in the blank: EPO is a _______ that is crucial for the production of red blood cells.

A

glycoprotein

168
Q

What is the clinical significance of dysregulation of EPO in serum?

A

Anemia, Polycythemia, Renal cancer, Renal failure

169
Q

What percentage of renal blood flow (RBF) is supplied by the kidneys?

A

20%-25% of cardiac output (CO)

170
Q

What does the term ‘normoxia’ refer to in relation to EPO synthesis?

A

Normal oxygen levels

171
Q

What is the primary role of prolyl hydroxylase domain (PHD) enzymes?

A

Regulate HIF activity in an O2-dependent manner

172
Q

What are the erythroid precursors involved in EPO signaling?

A

BFU-E, CFU-E, ProE, BasoE, PolyE, OrthoE, Retic

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
Q

What are the conditions associated with EPO levels in health and disease?

A

Normal, Anemias, Uremia, 2° Erythrocytosis, 1° Erythrocytosis

Uremia is a complication of chronic kidney disease and acute kidney injury.

174
Q

T or F: right-side diastolic heart failure does not exist.

175
Q

T or F: Right-side heart failure can happen independently of left-side function.

A

False: systolic failure is always assoc. w/ left-sided heart failure

176
Q

How is diastolic left-side heart failure quantitatively defined

A

preserved ejection fraction (50-70%)

177
Q

How is systolic left-side heart failure quantitatively defined

A

reduced ejection fraction (<49%)

178
Q

T or F: Plasma levels of ANP correlate w/ severity of symptomatic HF?

179
Q

T or F: ANP is secreted directly into the blood stream right after synthesis.

A

False
ANP is stored within granules of atrial cells and get released by external stimuli

180
Q

what are primary stimuli for ANP relase?

A

Atrial wall stretch

181
Q

what are secondary stimuli for ANP relase?

A

endothelin, Angiotensin II, AVP

182
Q

what are primary stimuli for BNP relase?

A

wall stretch and increased transmural ventricular pressure

183
Q

High concentrations of BNP in cardiac ventricles and circulation can indicate what cardiopathies

A

Ventricular HF
post-MI event

184
Q

Endothelial shear stress stimulates the release of what natriuretic peptides from vascular endothelium

185
Q

Describe the various pathways by which natriuretic peptide receptors are degraded?

A

Gi, Gq, neutral endopeptidases (Neprilysin)

186
Q

T or F: NPR-A has equal affinity for both ANP & BNP.

187
Q

NPR-B is specific for which NP

188
Q

What incretin stimulates the feeling of satiety

189
Q

what incretin is involved in the facilitation of triglyceride storage

190
Q

Prohormone convertase generates what?

A

alpha-cells
glucagon
GRPP
GLP 1 & 2
Glicentin
oxyntomodulin

191
Q

T or F: GLP receptors are Gs

192
Q

what incretin promotes beta-cell proliferation

193
Q

GLP-1Rs are densely expressed in what CNS tract?

A

Nucleus Tractus Solitarii

194
Q

GLP-1Rs are densely expressed in what nucelus?

A

paraventricular nucleus

195
Q

what role does calcitriol play int the endocrine kindy

A

vitamin D synthesis precursor

196
Q

T or F: during fetal development, EPO is primarily produced in the kidneys

A

False
mostly produced in hepatocytes

197
Q

During normoxia, EPO synthesis only occurs in what zone of the kindeys

A

inner cortex

198
Q

HIF-1alpha secretion is stimulated by low O2 levels and becomes the target of what enzyme

199
Q

Using your knowledge of Hemoglobin synthesis, what other proteins can you guess are upregulated in the presence of active PHD besides EPO

A

ferroportin
transferrin
VEGF-A

200
Q

What is the cellular response to EPO?

A

survival
proliferation
maturation

201
Q

Monomeric EPO receptors are only expressed on reticulocytes. T or F?

A

FALSE
they are only expressed on the cell membranes of erythroid progenitor cells

202
Q

What other incretin in conjunction w/ GLP also helps to stimulate satiety

A

oxyntomodulin

203
Q

What are the different types of adipose tissue?

A
  • Visceral (Intrabdominal)
  • Subcutaneous
  • Dermal
  • Femoral
  • Gluteal
  • Abdominal
  • Upper
  • Cranial
  • Gonadal
  • Perirenal
  • Omental
  • Mesenteric
  • Retroperitoneal
  • Epicardial

These depots exhibit distinct metabolic profiles and health implications.

204
Q

What is the relationship between upper body fat deposition and metabolic dysfunction?

A

Fat deposition in the upper body is linked to a higher risk of metabolic dysfunction

This includes visceral and subcutaneous abdominal fat.

205
Q

How does lower body adiposity relate to metabolic risk?

A

Lower body adiposity is associated with lower risk and may be protective

This includes subcutaneous, gluteal, and femoral fat.

206
Q

What are the constituents of adipose tissue aside from adipocytes?

A
  • Endothelial cells
  • Fibroblasts
  • Pericytes
  • Pre-adipocytes
  • Macrophages (pro- and anti-inflammatory)
  • Immune cells (T-cells, B-cells, PMNs)

Together, these are referred to as the adipose tissue stromal vascular fraction (SVF).

207
Q

What is the role of the adipose tissue stromal vascular fraction (SVF)?

A

SVF produces hormones and cytokines that can act in a paracrine manner

Alterations in SVF due to metabolic diseases is an area of active investigation.

208
Q

True or False: Women have a higher cardiometabolic risk associated with fat distribution than men.

A

False

Fat distribution in women is associated with lower cardiometabolic risk.

209
Q

What is the significance of gluteal and femoral depots in women?

A

These depots are more insulin-sensitive compared to visceral adipose tissue

They secrete more metabolically favorable adipokines such as adiponectin.

210
Q

What are homeobox genes?

A

Homeobox genes code for protein transcription factors

They exhibit expression patterns in fat depots due to differences in gene homeodomains.

211
Q

What are the different types of adipocytes based on color?

A
  • White adipose tissue (WAT)
  • Brown adipose tissue (BAT)
  • Beige adipose tissue

These types differ in their shape, size, and function.

212
Q

What is the primary function of white adipose tissue (WAT)?

A

Critical for energy storage, endocrine communication, and insulin sensitivity

WAT comprises the largest volume of adipose tissue.

213
Q

Where is brown adipose tissue (BAT) primarily located in adults?

A

In the supraclavicular and thoracic regions

BAT is metabolically active and contributes to whole-body fat oxidation.

214
Q

What induces the ‘beiging’ of white adipose tissue?

A
  • Diet
  • Exercise
  • Pre- and post-biotics
  • Pharmaceutical agents
  • Numerous plant-based bioactive compounds
  • Adipokines

Beiging may protect against obesity and associated metabolic dysfunction.

215
Q

What are uncoupling proteins (UCPs)?

A

Members of the mitochondrial anion carrier family that convert mitochondrial proton-motive force into heat

UCP1 is involved in adaptive thermogenesis.

216
Q

What triggers lipolysis in adipose tissue?

A

Mobilization of TAG when metabolic fuels are low and/or energy demand is high

This process is regulated by hormones and the sympathetic nervous system.

217
Q

What is leptin and its primary function?

A

A 16 kDa peptide hormone that regulates food intake (satiety)

It is primarily expressed in white adipose tissue.

218
Q

What are the forms of adiponectin?

A
  • Monomeric form
  • Globular form
  • Trimeric form
  • Hexameric form
  • Multimeric form

MMW and HMW oligomers make up most of the circulating adiponectin.

219
Q

What is the role of adiponectin in the body?

A

Increases insulin sensitivity and has anti-inflammatory effects

It inhibits liver fibrosis and is increased by thiazolidinediones.

220
Q

What receptors are involved in adiponectin signaling?

A
  • AdipoR1
  • AdipoR2
  • T-cadherin

They modulate insulin sensitivity and metabolic gene expression.

221
Q

What is the primary function of AdipoR2?

A

Modulates insulin sensitivity and metabolic gene expression in insulin-responsive tissues

AdipoR2 is involved in the activation of AMP-dependent protein kinase (AMPK), which promotes fatty acid oxidation.

222
Q

Which tissues express AdipoR2?

A

Skeletal muscle, liver

These tissues are critical for insulin responsiveness and metabolic regulation.

223
Q

What does T-cadherin activate?

A

PPARα via unidentified pathways

T-cadherin is found in cardiac myocytes, vascular endothelial cells, and smooth muscle cells.

224
Q

What is the primary effector of cardioprotection by adiponectin?

A

T-cadherin

Adiponectin is known for its protective effects on the heart, mediated through T-cadherin.

225
Q

What are small molecule activators of adiponectin signaling promising for?

A

Management of insulin resistance, NAFLD & T2D

These conditions are linked to metabolic dysregulation.

226
Q

Which pathways are involved in increasing glucose metabolism, fatty acid oxidation, and insulin sensitivity?

A

PPAR-α, AMPK, Ca++, CAMKK, PKC

These pathways play a significant role in metabolic regulation.

227
Q

What are the different forms of adiponectin mentioned?

A
  • LMW adiponectin
  • Globular adiponectin
  • HMW adiponectin

Each form may have distinct biological activities and effects.

228
Q

What is resistin and where is it predominantly secreted from?

A

A major adipose tissue-derived hormone, predominantly secreted from macrophages

Resistin is involved in inflammation and metabolic processes.

229
Q

What is the molecular weight of resistin?

A

Approximately 12.5 kDa

This size classifies it as a small protein.

230
Q

What are the effects of resistin?

A
  • Induces low-grade inflammation by stimulating monocytes
  • Induces insulin resistance
  • Inhibits differentiation of adipocytes in vitro

These effects contribute to metabolic dysfunction.

231
Q

Where are distinct patterns of resistin expression found?

A
  • Inguinal
  • Gonadal
  • Retroperitoneal
  • Mesenteric (WAT depots)
  • BAT

Each type of adipose tissue exhibits unique expression patterns.

232
Q

What inhibits the expression of resistin?

A

Thiazolidinediones (TZDs)

TZDs are a class of medications used to treat insulin resistance.

233
Q

Which two known receptors does resistin interact with?

A
  • Toll-like receptor 4 (TLR4)
  • Adenylyl cyclase-associated protein 1 (CAP1)

These interactions are crucial for resistin’s proinflammatory effects.

234
Q

True or False: Epidemiological, genetic, and clinical data support a role for resistin in dysfunctional metabolism and related pathologies.

A

True

This evidence highlights resistin’s potential impact on metabolic health.

235
Q

What is the therapeutic value of interventions to antagonize resistin action?

A

Remains undetermined in the treatment of metabolic or cardiovascular disease in humans

Further research is needed to clarify its therapeutic implications.

236
Q

what kind of cell signaling do adipocytes use?

237
Q

what AT receptors are ubiquitously expressed in all fat types and storage regions

238
Q

What ATRs are only expressed in white AT?

239
Q

AT in what regions of the body is densely expressed w/ A2 receptors

A

subcutaneous human AT

240
Q

What is the cellular effect of B3

A

stimulation of lipolysis

241
Q

what is the cellular effect of A2

A

inhibits lipolysis

242
Q

White APCs express what receptor on their surfaces

243
Q

Brown APCs express what receptor on their surface

244
Q

Myf5- APCs differentiates in to what type of adipocytes

245
Q

T or F: Adipose Tissue is derived from the endodermin

A

False
adipocytes have mesodermal origin

246
Q

T or F: adipocytes are derived from the myeloid linage of cells

247
Q

BMD-APCs are expressed in higher numbers for obese pts. What is the clinical significance of this?

A

BMD-APCs reduce expression of genes involved in lipid metabolism
they also increases gene expression of pro-inflammatory agents

248
Q

what are pink adipocytes and what is their function

A

high expression during pregnancy and throughout lactation
form milk-secreting alveoli
structure is more epithelia in nature

249
Q

T or F: White AT has the highest thermogenesis capability

A

FALSE
Brown AT has the greatest capacity for thermogenesis
seems to be correlated w/ # of mitochondria

250
Q

T or F: WAT has the greatest capacity to store lipids

251
Q

what type of APC expressess high levels of UCP1/thermogenin

252
Q

UCP3 is highly expressed in what tissue

A

skeletal muscle

253
Q

UCP4 & 5 are expressed where

254
Q

what conditions promote de novo lipogenesis

A

caloric restriction
adaptive thermogenesis

255
Q

how does insulin supress lipolysis

A

increasses activity of PDE3 and decreasing cAMP levels

256
Q

T or F: exercise is the major pro-lipolytic stimulus in humans.

A

THIS IS VERY TRUE AND THE MOST EFFEECTIVE WAY TO DECREASE BMI

257
Q

leptin is dysregulated in what malignancies

A

breast, endometrial, thyroid, GI

258
Q

T or F: leptin is underexpressed in break cancer ,malignancies

Endocrinology (9 decks)

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