Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacy Stage 3 - Endocrine System > Glucose, Glucagon and Diabetes > Flashcards

Glucose, Glucagon and Diabetes Flashcards

1
Q

what is glucose stored as?

A

glycogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

where are the 2 main sites for glucose storage?

A

muscle and liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is glucose used for in cells?

A

for metabolism/respiration - it is metabolised to give ATP for energy and H2O, CO2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the normal circulating blood glucose concentration?

A

~5mM (no matter how hungry you feel) as the glycogen will be broken down during times of low glucose to replace those used.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what hormone helps with the storage/uptake of glucose from the blood?

A

insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what hormone helps to release glucose from the stored tissue back into the blood?

A

glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

where are insulin and glucagon released from?

A

The Islets of Langerhans in the pancreas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q
  • What are the 3 main cell types in the islet of langerhan?

- What hormones do they release?

A
  • α cells – produce glucagon
  • β cells – produce insulin
  • γ cells – produce somatostatin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How is insulin sythesised?

A
  1. Made as a polypeptide in the beta cells
  2. The polypeptide chan is processed in the golgi to give pro-insulin which is biologically inactive
  3. Pro-insulin is activated by prohormone convertase 1 and 2 which removes 33 amino acids. These 33 amino acids make the C chain.
  4. Now we are left with the A and B chains with 30 and 21 amino acids respectively.
  5. The A and B chains are joined by disulfide bridges forming the insulin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is stored in the secretory granules of the beta cells?

A

the insulin along with some pro-insulin and c-peptide (the C-chain)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what happens in the 1st phase of insulin secretion?

A

elevated blood glucose levels causes stored insulin to be released from the secretory granules in the beta cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what happens in the 2nd phase of insulin secretion?

A

Synthesis of new insulin and then it’s released in elevated glucose levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what enzyme degrades insulin and where?

A

degraded by insulinase mainly in the liver but also in the muscle and kidneys

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is the half-life of insulin?

A

6minutes so its effects on tissues are rapidly reversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

how does glucose enter the beta-cells?

A

via the GLUT2 transporter system from the blood into the beta cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what determines the ATP concentration in the beta cells?

A

the concentration of glucose in the blood as that determines the amount of glucose that enters the beta-cell there determines how much glucose is metabolised to ATP.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Explain how glucose, K+ channels, and Ca2+ channels play a role in insulin secretion?

A
  1. Glucose enters beta-cell via GLUT2 transporter
  2. High glucose levels cause ATP levels to rise in the beta cell
  3. The K+ channels are ATP sensitive so a high ATP conc closes the K+ channel so K+ conc increases as it can’t leave the cell.
  4. This causes depolarisation of the membrane of the cell.
  5. The Ca2+ channels are then opened due to the depolarisation and Ca2+ enters
  6. this results in the release of insulin from the beta cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

why is the liver the major site for glucose storage?

A
  1. Once insulin is made by the pancreas, it i first drained into the hepatic portal vein therefore the liver is the first organ exposed to insulin
  2. The glucose from the gut is also transported to the liver via the portal circulation
    …..In this way, the insulin makes the liver store the glucose.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is the insulin receptor like on the target cells?

A

-dimeric with an alpha-subunit and a beta-subunit.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what happens when insulin binds to the alpha-subunit?

A
  1. it promotes dimerization and activation of the receptor

2. Once the receptors dimerise, then the 2 subunits phosphorylate each other at multiple tyrosine residues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Explain the process of insulin receptor signalling?

A
  1. Insulin binding causes receptor dimerisation/activation
  2. The 2 subunits phosphorylate one-another to become active
  3. Active receptors phosphorylate IRS-1
  4. IRS-1 activates PI3K
  5. PI3K stimulates cellular response to the insulin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what type of glucose transporter is found in the liver cells?

A

GLUT4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Where are GLUT4 transporters found in unstimulated cells of the liver?

A

in the intracellular membrane vesicles and not in the plasma membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is activated after PI3K in liver cells for insulin sensitivity?

A
  • The PI3K activates PKB
  • This evokes the translocation of the GLUT4 to the plasma membrane
  • This therefore allows glucose uptake into the hepatocyte
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How does glycogen synthesis occur?

A
  1. When GSK is active, the glycogen synthaseA is inactive, which prevents glycogen synthesis
  2. The GSK is inhibited by the PKB, which is activated by insulin. This therefore prevents glycogen synthaseA inhibition
  3. Therefore glycogen synthaseA is active and glycogen can be synthesised.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what happens when glycogen reserves in the liver are full and theres no more space to store glucose as glycogen?

A

the glucose is still able to enter the liver via the GLUT4 transporters, however, they are then metabolised into fatty acids which are released into the circulation and stored as fat eventually

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is the main source for cellular metabolism (respiration/ATP production) in the absence of insulin?

A

free-fatty acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

so why are people with type one diabetes likely to lose weight?

A
  • in the absence of insulin, the body is forced to use free-fatty acids (from fat) for respiration/energy.
  • however, in the presence of insulin, glucose is able to be taken up into cells to be used for energy.
  • therefore the free-fatty acids aren’t being used so they can be stored as fat.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

where does the CNS get its energy from?

A
  • CNS cells (the brain) can take up glucose without the need for insulin to be present.
  • this means it doesn’t metabolise fatty acids hence no lactic build-up in the brain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

how are fatty acids released from adipoctyte cells/tissue?

A
  1. Glucose does not enter the cell due to a lack of insulin
  2. This causes the hormone-sensitive lipase to breakdown the lipid molecule into 3 free fatty-acid chains and 1 glycerol molecule
  3. The fatty acids are then released to fuel metabolic processes.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

how does insulin prevent fatty acid release from adipocyte cells?

A
  1. insulin stimulates glucose entry into the cell via GLUT4 transporters
  2. Glucose is metabolised to glycerol once in the cell
  3. The glycerol binds to the 3 free fatty acids to form the triglyceride lipid. (the fatty acids come from the blood and enter the cell)
  4. Insulin also inhibits the lipase enzyme which usually breaks down the lipid
32
Q

how does insulin promote new protein synthesis?

A
  1. The rise in amino acid levels in the blood promotes insulin release from β cells
  2. Insulin receptors activates a second PI3K- dependent kinase
  3. This PI3K- dependent kinase activates Target Of Rapamycin Complex 1 (TORC1), which is a central regulator of protein synthesis in essentially all cells
  4. When amino acids are abundant, insulin stimulates their incorporation into protein
33
Q

where is glucagon secreted?

A

from the pancreatic alpha cells

34
Q

how many amino acids is glucagon made from?

A

29 amino acids

35
Q

how does glucagon work to increase blood glucose?

A

it promotes the release of glucose from the liver

36
Q

why is glucagon released during exercise?

A

To promote the uptake of skeletal muscles by translocating GLUT4 transporters to the surface of the muscle cells

37
Q

what type of receptor is the glucagon receptor?

A

G protein-coupled receptor, coupled to Gs and activates the cAMP / PKA-dependent signalling pathway.

38
Q

What hormone can activate the glucagon pathway to promoting glucose release from liver, and what receptor is activated this way?

A

Adrenaline via β adrenoceptors.

39
Q

How does glucagon cause the release of fatty acids from adipose tissue?

A

Glucagon activates the hormone sensitive lipase enzyme to breakdown triglycerides to release the fatty acids.

40
Q

what can raise both insulin and glucagon levels?

A

amino acids

41
Q

What happens when insulin and glucagon are released due to high amino acid levels?

A
  • insulin secretion promotes increase in amino acid uptake by cells, but also promotes a reduction of plasma glucose
  • glucagon secretion will promote an increase in plasma glucose, but glucagon has no effect on amino acid uptake
42
Q

Once glycogen stores are depleted what happens to meet the demand for glucose?

A

glucagon stimulates the formation of glucose from lipids and amino acids via complex metabolic processes in liver and kidney called
“gluconeogenesis”

43
Q

what is normal fasting blood glucose?

A

~5mM

7mM or more = diabetes

44
Q

how can urine help to see if a patient is diabetic?

A

if sugar is present in the urine, then that indicates diabetes

45
Q

what tissues are damaged by chronic high blood glucose levels?

A

blood vessels, eyes, kidneys, nerves - almost all tissues

46
Q

what happens to the body if the patient has untreated type 1 diabetes?

A

Untreated type 1 diabetes leads to body wasting

47
Q

how does insulin cause type 1 diabetes?

A

a failure of insulin secretion

48
Q

how does insulin cause type 2 diabetes?

A

insulin resistance in tissues

49
Q

which of the 2 types of diabetes is gradual onset and which is sudden onset?

A

gradual onset = type 2

sudden onset = type 1

50
Q

which of the 2 types of diabetes is associated with obesity?

A

type 2

51
Q

what is gestational diabetes?

A

High blood glucose that develops during pregnancy and tends to disappear after birth

52
Q

during what trimester does gestational diabetes occur?

A

2nd or 3rd

53
Q

how does gestational diabetes occur?

A

when Beta-cells cannot produce enough insulin to meet the extra- needs in pregnancy

54
Q

what are the possible consequences of gestational diabetes?

A
  • Baby growing larger than usual
  • Premature birth (before 37th weeks)
  • Pre-eclampsia (high blood pressure which can lead to complications in pregnancy)
  • Jaundice after birth
  • An increased risk to develop type 2 diabetes in future
55
Q

what is the pathogenesis of type 1 diabetes?

A
  1. Beta cells are recognised by T-cells because the insulin peptides form a complex with MHC molecules on the surface of the beta cells
  2. This results in an autoimmune mechanism where CD8 cytotoxic T cells mediate the destruction of beta-cells
  3. This results in the failure of insulin secretion
56
Q

what are the symptoms of diabetes due to a lack of insulin?

A
  1. Tissues cannot accumulate and store glucose
  2. Tissues cannot use glucose as metabolic fuel so will use proteins and fatty acids resulting in rapid weight loss
  3. Body cannot store excess energy as fat therefore weight loss
  4. Reduced synthesis of protein
  5. Formation of ketones resulting in metabolic acidosis causing an acidotic coma
  6. Hyperglycaemia
57
Q

how does hyperglycaemia affect the kidneys to cause dehydration?

A
  1. High [Glucose] enters glomerular filtrate and overwhelms glucose absorbing capacity of proximal convoluted tubule
  2. Increased fluid osmolarity in tubules
  3. More water is secreted from cells into the proximal convoluted tubule
  4. causes increased urine flow – diuresis - and reduced water reabsorption
  5. This results in Dehydratation, excessive urine production and thirst
58
Q

what is used to treat type 1 diabetes?

A

Insulin

59
Q

what circulation does natural and exogenous insulin enter?

A
  • Natural insulin enters hepatic circulation

- exogenous insulin enters main/general circulation

60
Q

how does insulin injection cause lipohypertrophy?

A

insulin promotes the deposition of fat therefore cells close to site of insulin injection are exposed to high [insulin]. If the same site is used everytime time, it will promote the deposition of fat around injection site (lipohypertrophy)

61
Q

what is the downside of lipohypertrophy besides it being unpleasant to the eyes.

A

leads to an unpredictable rate of insulin absorption. This could lead to poor glycaemic control and patients could experience hyper/hypoglycaemic events.
Therefore it is important to change site of injection frequently

62
Q

what are the 3 forms of insulin used for therapy?

A
  1. Animal insulin (porcine/bovine)
  2. Human insulin
  3. Human insulin analogue
63
Q

what are the 3 types of human insulin?

A
  1. soluble insulin - rapid and short-lived
  2. Isophane insulin - intermediate acting, forms precipitates
  3. Insulin zinc suspension - Long acting, forms precipitates
64
Q

what are the 2 types of insulin analogues?

A
  1. Insulin Lispro

2. Insulin glargine

65
Q

How is insulin lispro obtained and how long does it last?

A
  • obtained by switching a lysine and a proline residue

- very rapid and very short lived so taken just before meals

66
Q

How is insulin glargine obtained and how long does it last?

A
  • obtained by mutating Asn21 in Gly and by adding 2Arg at the end of the B chain
  • Long-acting so normally taking before a meal in combination with a short-acting form
67
Q

what drug targets the autoimmune reaction in diabetes 1?

A

Teplizumab

68
Q

what is the pathogenesis of type 2 diabetes?

A
  1. Genetic and environmental
    predisposition e.g. Life style, Bad dietary habits, Obesity
  2. Insulin resistance therefore reduced glucose uptake
  3. Hyperinsulinemia
  4. β cells failure and hypoinsulinemia (β cells cannot keep up with the peripheral demand of insulin so Insulin secretion decreases)
  5. Diabetes occurs as total failure of insulin secretion occurs
69
Q

What 4 factors of obesity cause insulin resistance?

A
  1. Free-fatty acids
  2. Adipokines
  3. Inflammation
  4. PPARγ
70
Q

what is 1st line therapy for type 2 diabetes?

A

diet and exercise - to reduce weight and reverse the development of normal sensitivity of insulin

71
Q

what can be possibly used to treat type 2 diabetes during the disease?

A
  1. Thiazolidinediones (TZD) e.g. pioglitazone
  2. Metformin
  3. Sulphonylureas (e.g. gliclazide)
  4. α glucosidase inhibitors (Acarbose)
  5. Insulin
  6. α2 adrenoreceptor antagonists
  7. Selective β3 agonists
72
Q

How does increased glucose and free fatty acids cause microvascular complications?

A

They cause microvascular vascular complications which can cause nephropathy and retinopathy, therefore resulting in macrovascular complications

73
Q

how is AGEs formed?

A
  1. sugar + protein = schiff base
  2. Schiff base —> amadori products
  3. Amadori products —-> AGEs
74
Q

What are the biological effects of AGEs?

A
  1. CVD
  2. Diabetes
  3. Kidney disease
  4. Sarcopenia
  5. Rheumatoid arthritis
  6. Alzheimers disease
75
Q

how does AGEs cause blood vessel damage?

A
  1. AGE’s crosslinks with collagen
  2. The basal membrane of the endothelium thickens
  3. The thickened endothelium traps LDL and IgGs
  4. Oxidation, complement activation and inflammation
  5. Blood vessel damage
76
Q

what are microvascular diseases?

A

Formed from damage to small blood vessels:

  1. retinopathy
  2. nephropathy
  3. neuropathy
77
Q

What are macrovascular diseases?

A

Damage to medium to large blood vessels:

  1. Coronary artery disease
  2. Cerebrovascular disease
  3. peripheral vascular disease

Pharmacy Stage 3 - Endocrine System (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions