Receptor Tyrosine Kinases and Insulin Flashcards

1
Q

What is the first form of insulin synthezised in the body?

A

Pre pro-insulin

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2
Q

What are the components of pre-pro-insulin?

A

A signal sequence, A chain , B chain and C peptide

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3
Q

What is the molecular weight of insulin?

A

Approximately 6000 Daltons

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4
Q

What happens to pro-pro-insulin in the endoplasmic reticulum?

A

The signal sequnce is cleaved to form proinsulin

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5
Q

What stabilizes the structure of proinsulin?

A

Disulfide bonds(S-S bonds) betwen the A and B chains.

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6
Q

What happens to proinsulin in the Golgi apparatus?

A

The C peptide is cleaved,forming mature insulin.

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7
Q

What are the components of mature insulin?

A

A chain( 21 amino acids)
B chain(30 amino acids),connected by disulfide bonds.

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8
Q

Why is the 3D structure of insuli important?

A

It is essential for binding to the insulin receptor and ensuring biological activity.

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9
Q

Where does the conversion of pre-pro-insulin to proinsulin occur?

A

In the endoplasmic reticulum

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10
Q

Where does the conversion of proinsulin to mature insulin occur?

A

In the Golgi Apparatus

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11
Q

What are the Islets of Langerhans?

A

Clusters of endocrine cells in the pancreas that regulate glucose homeostasis

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12
Q

Approximately how many islets of Langerhans are in the pancreas?

A

Around 1 million islets, constituting 1-1.5% of pancreatic tissue

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13
Q

What is the primary function of the islets of Langerhans?

A

To regulate blood glucose levels by secretin hormons like insulin,glucagon and somatostatin.

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14
Q

What are the main cell types in the Islets of Langerhans?

A

Beta cells
Alpha cells
Delta cells

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15
Q

What hormone is secreted by beta cells,and what is its function?

A

Hormone : Insulin
Function:Lowers blood glucose by promoting glucose uptake in tissues

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16
Q

What proportion of the Islet cells are beta cells?

A

About 60%

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17
Q

What hormone is secreted by alpha cells, and what is its function?

A

Hormone : Glucagon
Function: Raises blood glucose by stimulating glycogen breakdown and gluconeogenesis in the liver

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18
Q

What portion of the islet cells are alpha cells?

A

Approximately 20%

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19
Q

What hormone is secreted by delta cells and what is its function?

A

Hormone: Somatostatin
Function: Regulates and inhibits the secretion of insulin and glucagon it also controls gastrointestinal processes

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20
Q

What proportion of the Islet cells are delts cells?

A

About 10%

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21
Q

What do the red,green and blue signals represent in the immunofluorescence image of the islets?

A

Red:Insulin-producing B-cells.
Green:Glucagon-producing a-cells.
Blue:Nuclear staining (all cells)

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22
Q

What seperates the endocrine islet cells from the exocrine pancreas tissue?

A

A distinct boundary visisble under microscopic and immunofluorescent imaging

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23
Q

What is the role of somatostatin in the pancreas?

A

To fine-tune hormone secretion by inhibiting insulin and glucagon release.

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24
Q

where are the islets of Langerhands located within the pancreas?

A

Scattered throughout the pancreatic tissue, surrounded by exocrine cells.

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25
Q

What transporter is repsondsible for glucose entry into pacreatic B cells?

A

The GLUT2 transporter

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26
Q

What enzyme phosphorylates glucose inside B-cells?

A

Glucokinase

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27
Q

What happens to glucose after it is phosphorylated in b-cells?

A

It enters glycolysis and oxidative phosphorylation,generating ATP.

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28
Q

How does an increase in ATP/ADP affect ratio ATP-sensitive potassium channels

A

ATP binds to these channels, causing them to close.

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29
Q

What is the effect of closing ATP-sensitive K⁺ channels?

A

It causes membrane depolarization by preventing K⁺ efflux.

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30
Q

What channels open as a result of membrane depolarization?

A

Voltage-gated calcium (Ca²⁺) channels.

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31
Q

What is the role of calcium ions (Ca²⁺) in insulin secretion?

A

Calcium influx triggers insulin-containing storage granules to fuse with the membrane, leading to exocytosis of insulin.

32
Q

What is the final step in insulin secretion?

A

Insulin is released into the bloodstream via exocytosis.

33
Q

What process links glucose metabolism to insulin secretion in β-cells?

A

The rise in the ATP/ADP ratio, which closes K⁺ channels, depolarizes the membrane, and opens Ca²⁺ channels.

34
Q

What is the clinical relevance of insulin secretion?

A

Dysfunctions in this process can lead to conditions such as diabetes mellitus.

35
Q

What triggers the fusion of insulin storage granules with the cell membrane?

A

The influx of calcium ions (Ca²⁺) into the β-cell.

36
Q

What role does GLUT2 play in insulin secretion?

A

GLUT2 allows glucose uptake into β-cells, initiating the secretion process.

37
Q
A
38
Q
A
39
Q

What happens to the ATP-sensitive K⁺ channel under low glucose conditions?

A

It remains open, allowing K⁺ efflux and maintaining the resting membrane potential.

40
Q

What is the relationship between depolarization and calcium influx in β-cells?

A

Depolarization causes the opening of voltage-gated Ca²⁺ channels, allowing calcium influx.

41
Q

What are receptor tyrosine kinases (RTKs)?

A

RTKs are cell surface receptors that act as both receptors and enzymes, playing a critical role in cell signaling for growth, differentiation, and survival.

41
Q

What are the three main structural components of RTKs?

A

Extracellular ligand-binding domain
Transmembrane α-helix
Intracellular kinase catalytic site

41
Q

What is the function of the extracellular domain of RTKs?

A

It binds specific ligands, such as growth factors (e.g., insulin, EGF).

42
Q

What is the role of the transmembrane α-helix in RTKs?

A

It spans the plasma membrane and connects the extracellular domain to the intracellular kinase domain.

43
Q

What is the function of the intracellular kinase domain in RTKs?

A

It phosphorylates tyrosine residues on the receptor itself or other proteins, enabling signal transduction.

44
Q

What type of residue is phosphorylated by RTKs?

A

Tyrosine residues.

44
Q

What happens when a ligand binds to an RTK?

A

The receptor undergoes dimerization.
The kinase domain becomes active and performs autophosphorylation.

45
Q

What is autophosphorylation in RTKs?

A

The process where the kinase domain phosphorylates tyrosine residues on its own cytoplasmic tail.

46
Q

How does RTK phosphorylation propagate a signal?

A

Phosphorylated tyrosines act as docking sites for intracellular signaling proteins, initiating downstream pathways like MAPK or PI3K/AKT.

47
Q

Why are RTKs important in biomedical science?

A

RTKs regulate critical processes like growth and metabolism. Dysregulation of RTKs is associated with diseases like cancer and diabetes.

48
Q

What is the role of RTKs in cancer?

A

Overactive RTKs can lead to uncontrolled cell proliferation and tumor growth.

49
Q

Name two key signaling pathways activated by RTKs.

A

The MAPK pathway and the PI3K/AKT pathway.

50
Q

What happens when ATP binds to the kinase domain of an RTK?

A

The RTK phosphorylates tyrosine residues, activating downstream signaling proteins.

51
Q

What is the structure of the insulin receptor?

A

The insulin receptor is a heterotetramer composed of:

Two α-subunits (130 kDa, 735 amino acids).
Two β-subunits (95 kDa, 620 amino acids).

52
Q

What links the α- and β-subunits in the insulin receptor?

A

Disulfide (S-S) bonds.

53
Q

Where are the α-subunits of the insulin receptor located, and what is their function?

A

Location: Extracellular.
Function: Contain the hormone-binding domains that bind insulin.

54
Q

What is the role of the β-subunits in the insulin receptor?

A

They span the membrane and extend into the cytoplasm.
Contain the ATP-binding domain and tyrosine kinase domain for signaling.

55
Q

What happens when insulin binds to its receptor?

A

The receptor undergoes a conformational change.
The tyrosine kinase domain in the β-subunits becomes active.
Autophosphorylation occurs, initiating downstream signaling.

56
Q

What is the primary function of the insulin receptor?

A

To regulate glucose uptake, metabolism, and other cellular responses.

57
Q

What type of receptor is the glucagon receptor?

A

A G-protein-coupled receptor (GPCR).

58
Q

What is the structure of the glucagon receptor?

A

It has seven transmembrane helices and extracellular and intracellular domains.

59
Q

What happens when glucagon binds to its receptor?

A

The receptor activates an associated G-protein.
G-protein activation triggers downstream signaling, such as cAMP production.

60
Q

What is the primary function of the glucagon?

A

To promote glucose release from the liver during fasting.

61
Q

How does the insulin receptor signaling differ from glucagon receptor signaling?

A

Insulin receptor: Uses tyrosine phosphorylation for signaling.
Glucagon receptor: Activates G-proteins and increases cAMP.

62
Q

What clinical condition is associated with insulin receptor dysfunction?

A

Insulin resistance,a hallmark of type 2 diabetes.

63
Q

How can dysregulation of the glucagon receptor contribute to diabetes?

A

Overactivation of the glucagon receptor can lead to excess glucose release,worsening hypergycemia.

64
Q

What are the main ligands for the insulin and glucagon receptors?

A

Insulin receptor: Insulin.
Glucagon receptor: Glucagon.

65
Q

What is the B adrenergic receptor?

A

It is a G protein couples receptor that responds to catecholamins like adrenaline and nonadrrenaline

66
Q

How many transmembrane helices does the β-adrenergic receptor have?

A

It has seven transmembrane helices.

67
Q

What is the function of the extracellular side of the β-adrenergic receptor?

A

It contains the ligand-binding site, where molecules like adrenaline bind.

68
Q

What happens when a ligand binds to the β-adrenergic receptor?

A

The receptor undergoes a conformational change and activates intracellular G-proteins.

69
Q

Which G-protein is associated with the B adrenergic receptor?

A

The receptor activates Gs protein(stimulatory G-proteins).

70
Q

Which G-protein is associated with B adregenergic recepto>

A

The receptor activates Gs proteins(stimulating G-proteins).

71
Q

What signalling molecule is produced when Gs proteins are acivate?

A

Cyclic AMP (cAMP) is produced.

72
Q

What is the role of cAMP in β-adrenergic receptor signaling?

A

cAMP activates protein kinase A (PKA), which phosphorylates target proteins to elicit physiological responses.

73
Q

What are the physiological effects of β-adrenergic receptor activation in the heart?

A

Increases heart rate and contractility (β1 receptor subtype).

74
Q

What is the physiological effect of β-adrenergic receptor activation in the lungs?

A

Causes bronchodilation (β2 receptor subtype).