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reg Flashcards

1
Q

In addition to obesity which other conditions are associated with the metabolic syndrome

A

Cardiovascular disease
Renal failure
Dyslipidemia
Hypertension (high blood pressure)

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2
Q

Above what BMI levels is someone classed as obese?

A

> 30

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3
Q

In 2018 the proportion of children (11-15 years of age) within the UK that were classed as overweight or obese was?

A

20%

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4
Q

Obesity is a heterogeneous group of conditions with multiple causes that can be influenced by

A

Enviromental factors

Genetics

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5
Q

Obesity is associated with increased risk of

A

Type 2 diabetes
Stroke
Dementia

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6
Q

The hypothalamus can influence energy balance and body weight by changing

A

Behaviour
Neuroendocrine system
Autonomic nervous system activity

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7
Q

Satiation signals can influence energy intake by

A

suppressing appetite

slowing gastric emptying

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8
Q

Brown adipose tissue (BAT) is found

A

in babies as well as along the spine

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9
Q

Brown adipose tissue gets its colour due to

A

tightely packed mitchondira

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10
Q

The main uncoupling protein expressed within the mitochondria of adipocytes involved in adaptive thermogenesis is

A

UCP1

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11
Q

Rodent models of monogenic obesity led to the discovery of which hormone

A

Leptin

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12
Q

The obesogenic phenotype of the db/db mouse can be rescued by the injection of leptin

A

False

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13
Q

Leptin in an afferent hormone released from

A

adipocytes

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14
Q

Which of the following is the only orexigenic hormone

A 
Leptin
Ghrelin
Insulin
Adiponectin
(ghrelin)
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15
Q

What are three funtions of leptin

A

Memory formation
Immune response
Reproductive hormone balance

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16
Q

Second order neurons begin in the

A

LHA, PVN

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17
Q

what is the product of sequential cleavages of Pro-opiomelanocortin (POMC)?

A

alpha MSH

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18
Q

name three similarites between leptin and insulin

A

Circulates in proportion to adiposity
Is an anorexigenic hormone
Has a specialised transport system into the brain

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19
Q

The hypothalamus is a brain region central to

A

survival

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20
Q

Leptin and Insulin receptors are expressed highly in the

A

ARC (in the brain)

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21
Q

NPY and AgRP produce which type of response?

A

Orexigenic

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22
Q

Alpha MSH produces which type of response?

A

Anorexigenic

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23
Q

what is Anorexigenic

A

decrease food intake

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24
Q

What is Orexigenic

A

increaase food intake

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25
Q

Agouti is ectopically expressed in the Ay mouse model. In the brain it binds to the AgRP receptor …

A

MC3/4R

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26
Q

Why is recombinant leptin therapy not a viable treatment for the majority of obese patientsImmersive Reader

A

They already have high blood leptin levels

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27
Q

What is the most common cause of obesity

A

mutations in the MC4R

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28
Q

What are the Two main ideas for leptin resistance

A

prevention of leptin activation

impared transport of leptin into the brain

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29
Q

What three proteins are activated by leptin siganlling

A

JAK2-STAT3
AMPK
PI3K

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30
Q

PTP1B is a

A

Phosphatase

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31
Q

SOCS3 expression is decreased in mouse models of obesity true of false

A

false

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32
Q

what are three mouse models for obesity

A

Fatty rat
Ob/Ob
DIO

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33
Q

Mutations in what genes have been idetified with human genetic obesity

A

POMC
PC-1
MC4R

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34
Q

what is a common side effect of obesity drugs

A

cardiovasuclar events

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35
Q

what was for a long time the only drug approved to treat obesity

A

orlistat

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36
Q

what are three drugs used to treat obesity

A

Rimonabant
Lariglutide
Qsymia

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37
Q

The average weight loss with Bariatric surgery is

A

50-60%

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38
Q

what is the only drug allowed ot treat obeisty in the US

A

Lorcaserin

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39
Q

Give an exmaple of something that inhibts GH secreation by the pituitary

A

increased blood glucose

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40
Q

what transcribes the GW gene in somatotrophs

A

Pit-1

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41
Q

what are the hormones commanly assosiated with regulating growth

A

Thyroid Hormone
Testosterone
Growth Hormone
IGF-1

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42
Q

What are the four important name and strucutre facts about GH

A

It has a half-life of 25-30 min in the blood circulation
Has a molecular size of ~20-22 kDa
Secreted in a pulsatile manner from the pituitary gland
Also known as somatotropin

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43
Q

what are the consequnces of GH action

A

Increased hepatic IGF-1 production
Increased cellular protein synthesis
Spared utilisation of glucose as a metabolic fuel
Increased lipolysis

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44
Q

___(# )____ molecule(s) of GH bind(s) to ___(# )____ receptor(s). Signal transduction follows which leads to the production of _____. This signaling occurs via the ______ family of intracellular tyrosine kinases and the ______ family of transcription factors.

A

One; Two; IGF-1; JAK; STAT

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45
Q

what IGF-1 binding proteins is the carrier for the IGF-1 in plasma for promoting somatic growth

A

IGF-3 BP1

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46
Q

Acromegaly is assoated with what

A

the continoues secreation of GH in adualts

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47
Q

hyperplasia is what

A

increased cell production

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48
Q

what conditions result in a short height

A

Hyposecretion of Growth hormone-releasing hormone
Failure to generation IGF in the liver
Growth hormone receptor deficiency

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49
Q

where are glucagon and trypsin made

A

Glucagon - Alpha Cells (Source)

Trypsin - Acinar Cells (Source)

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50
Q

what is the name given to insulin resistance/lack

A

Diabetes Mellitus

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51
Q

what K channels are important for the funtion of beta cells

A

K-ATP channels

52
Q

Alpha cells are found in _________ of the islet while beta cells are usually found in the __________ of the islet

A

Periphery, Centre

53
Q

Somatostatin will inhibt secreation of

A

insulin, glucagon, GH

54
Q

how is insulin manufactured

A

in a pre pro form in the alpha cells

55
Q

when is pancreatic glucagon release stimulated

A

in hypoglycemai

56
Q

what dose insulin release need

A

an increase incytoslic release

57
Q

what dose glycgon bind to in the liver

58
Q

where is pancreatic polypeptide secreated

A

by F cells in the endocrone portion of the islets of langergnas

59
Q

what dose hyposecreation of insulin cause

A

Diabetes Mellitus
Hyperglycemia
Increased gluconeogenesis

60
Q

what stimulates insulin release

A

Increase in blood glucose
Increase in amino acids
Increase in sympathetic neural activity

61
Q

can someone live without a pancrease

62
Q

what transporter mediates the transfer of fructose across mammalina cell membranes

A

GLUT2 and GLUT 5

63
Q

what drives glucose transport by GLUT2 across the cell membrane

A

glucose chemical gradient

64
Q

what GLUT transporter are in class 1

A

GLUT1,3,4 are high affinity binding proteins with GLUT2 low affinity

65
Q

what GLUT transporter are in class 2

A

GLUT5,7,9,11 have low glucose affinity and transport fructose

66
Q

what GLUT transporter are in class 3

A

GLUT6,8,10,12

67
Q

what are two things about Cytochalasin B

A

it is a fungal metabolite and binds to glucose in a 1:1 ratio

68
Q

what is the insulin receptor made up of

A

an alpha and beat subunit with the alpha completely extracelluar and the beta a single transmembrane

69
Q

How are the alpha and beta of the insulin receptor bound toghether

A

by disulphide bonds

70
Q

what are the substrates for phosphoinositide 3-kinase (PI3K)?

A

Phosphatidyl inositol

Phosphatidyl inositol 4,5 bisphosphate

71
Q

Protein Kinase B is phosphorylated and activated by___________and ___________on ________ and __________residues, respectively

A

PDK1; mTORC2; Thr308; Ser473

72
Q

what dose exersies stimulate to increase GLUT 4 translocation

73
Q

What stimules activates AMPK

A

Exercise
AMP
Metformin
AICAR

74
Q

what dose metoformin do 3 things

A

Stimulates glucose uptake in skeletal muscle
Inhibits hepatic gluconeogenesis
Stimulates AMPK

75
Q

what kinase is important in insulin siganl tranduciton

76
Q

Insulins activaty on GSK3 is

A

activation

77
Q

what kind of kinase is the insulin receptor

78
Q

when insulin binds to its receptor what happens

A

there is a confomational shift and autophosphorylation of the receptor as well as binding of singnalling protiens that mediate signlling

79
Q

PI3 kinase phosphoralytes what

A

phospholipids

80
Q

what dose glucagon act through

81
Q

metformin needs beta cells to work T F

82
Q

what action dose metformin have on the body

A

inhibits gluconegenesis and increases glucose uptake

83
Q

how dose metformin enter the cell

A

through the OTC1 transporter

84
Q

how is AMPK activated by metformin

A

inhibits complex 1 that casues NADH to ATP ratio to change activaitng the AMPK

85
Q

Sulphonylureas do what

A

promote insulin secretion by blocking the ATP-sensitive K channel like ATP causing an AP form and insulin to be released

86
Q

Glucagon effects

A

increase blood glucose through increased glycogenolysis and gluconeogenesis and supressing glycolysis

87
Q

insullin action in adipose tissue

A

supress breakdown of triglycerides

88
Q

glucagon action in adipose tissue

A

increases breakdown of triglycerides

89
Q

SGLT2 what are they

A

work in the kidneys for the reabsorbtion of glucose fomr the urine used for tpye 2

90
Q

what rate is glucose saturation

91
Q

what do SLGT 2 inhibitors casue for weight

A

weight loss as due to osmolarity the water is drawn away form the urine

92
Q

Thiazolidinediones what dose it do

A

increases glucose uptake in sketal muscels and decreases glucose release by the liver

93
Q

Glucagon-like peptide (GLP)-1 agonist funtion

A

increase expression of incretins

94
Q

what are incretins

A

released after a meal supress appettie and increase insulin secreation

95
Q

DPP-4 inhibitors

A

block the action of DPP-4 that inactives the incretins

96
Q

what GLP-1 agonists types are there

A

types fast acting (liraglutide) > 24hr and slow (exenatide) <24hr

97
Q

DPP-4 side effects

A

do not cause weight gain and will reduce HbA1c by 0.43-1.47 % but do not increase cardiovascular events and may reduce blood pressure and also carry a low risk of hypoglycaemia

98
Q

GLP-1 effects

A
  • Β-cells in the pancreas enhance glucose dependant insulin secretion
  • Α-cells in the pancreas supresses the postprandial (after eating) glucagon secretion
  • In the liver it reduces hepatic glucose output
  • Slows the rate of gastric emptying in the stomach
  • In the brain reduces appetite and promotes feeling full
99
Q

what are the main funtions of the kidney get 5 out of all

A
  1. Maintain water balance
  2. Maintain proper osmolarity
  3. Regulate quantity and concentration of extracellular fluid ions Na, K
  4. Maintaining plasma volume
  5. Maintain acid-base balance
  6. Excretion end products of bodily metabolism
  7. Extracting foreign compounds
  8. Producing erythropoietin
  9. Making renin
  10. Converting vit D to an active form
  11. Glucose homeostasis
100
Q

look up the strucure of the kidney and its funtion

101
Q

look up insulin siganlling and thoughts

102
Q

look up renal singanlling

103
Q

Systemic arteries , arterioles and capillaries

A

carry oxygenated blood form the left ventricle to systemic organs

104
Q

Systemic veins, venules and capillaries

A

carry deoxygenated blood and waste from periphery towards the right atria

105
Q

what are the three main layers of ariters

A

intima
media
Adventitia/externa

106
Q

descirbe the intima

A

is the blood facing layer and is made up of endothelial cells + subendothelial space and is a single cell layer and acts as a barrier to pathogens in the blood and communicate to the vascular smooth muscle to regulate diameter

107
Q

describe the media

A

made of vascular smooth muscles and will change the diameter

108
Q

descibe the Adventitia/externa

A

– a collagen rich layer with sympathetic nerves are found as well as elastic and a vaso vasorum ( for capillaries to embed in the layer)

109
Q

veins intma

A
  • endothelial cells
110
Q

veins Media

A

– small amounts of vascular smooth muscle

111
Q

veins Externa-

A

thicker than arteries and is less elastic

112
Q

what are the four hormones that regulate vascualr tone

A

hormones nitric oxide, endothelial derived hyperpolarising factor (EDHF), endothelin-1 (ET-1) and angiotensin II

113
Q

where is nitric oxide sythesised

A

endothelial cells where it will then pass through the sub-endothelila space

114
Q

what is the role of nitric oxide

A

activate the guanylyl cyclase that will convert GTP to cGTP activating the PKG causing the relaxation of the smooth muscles

115
Q

what activates nitirc oxide production

A

A GPRC will be stimulated by a ligand (Ach) activating a phosphorylation cascade causing intracellular Ca to be released activating the calmodulin that will then cause synthesis of NO from arginine

116
Q

how dose EDHF cause vasodilation

A

cause a K efflux to relax the muscels

117
Q

ET-1 effect

A

vasoconstriction where after getting made in a prepro form it also inhibits NO bioavability and promotes inflamation

118
Q

Angiotensin II causes

A

causes smooth muscle contraction via the GPCR and Ca release

119
Q

what four things increase type 2 diabetes risk

A

obesity, dyslipidaemia , rasied blood pressure and raised blood glucose

120
Q

look at therpaies for vascular dyfuntion

121
Q

Atherosclerosis 5 stages are

A
  1. Endothelial dysfunction
  2. Immune cell infiltration
  3. Fatty streak
  4. Young plaque
  5. Unstable plaque
122
Q
  1. Endothelial dysfunction is what
A

there is a loss in enothelium-dervied vasomotor control well lower NO and greater ET-1 those that have it also have high cell permeability, high chemokine and cytokine secretion

123
Q

Immune cell infiltration

A

– this is were immune cells infiltrate the sub-endothelial space you will find increased adhesion molecules on endothelial cells eg ICAM-1,VCAM-1

124
Q

Fatty streak

A

this is where more ox-LDL (Oxidized low-density lipoprotein) are found in the sub-endothelial and phagocytosis of ox-LDL by macrophages occurs. It is seen as a fatty streak on the lumen

125
Q

Young plaque

A

Foam cells accumulate and fibrous cap thins as the fat increases and the fibrous cap ( barrier into the blood ) thins

126
Q

Unstable plaque

A

– the plaque becomes unstable and will start to calcify as well as becoming likely to rupture

Regulatory (2 decks)

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