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MD1 Metabolism > Insulin Signal Transduction > Flashcards

Insulin Signal Transduction Flashcards

1
Q

What do receptors binding hormone trigger in the target cell?

A

Intracellular signalling events

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2
Q

What do the signalling events in the cell do?

A

Control target cell responses

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3
Q

What is the only source of insulin in the body?

A

Beta pancreatic cells

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4
Q

Why is the insulin gene expressed in beta pancreatic cells and not in otherss?

A

Gene in open state in beta pancreatic cells, whereas in other cells gene in closed state

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5
Q

What controls whether the insulin gene is in an open or closed state?

A

Different patterns of histone modification

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6
Q

Other than histone modification, what else controls insulin expression in beta pancreatic cells?

A

Transcription factors bind to promoter and enhancer elements (= key DNA elements) upstream to transcription start site > regulate access of RNA polymerase II to insulin gene

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7
Q

What is the post-translational processing of insulin?

A

Preproinsulin translated > signal sequence cleaved > proinsulin > C peptide cleaved > insulin

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8
Q

Why is the beta pancreatic cell at risk from stress events associated with high protein synthesis and release?

A

Because of high secretory load

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9
Q

What is glucagon-like peptide-1 (GLP-1)?

A

Endogenous regulator released from gut cells in response to glucose and other nutrients in lumen

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10
Q

What does GLP-1 do?

A

Releases insulin in Ca-independent way via amplifying cAMP production

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11
Q

What are sulphonyl ureas?

A

Exogenous drugs

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12
Q

What do sulphonyl ureas do?

A

Close ATP-gated K channels in beta cells in glucose independent way

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13
Q

Other than glucose, what else affects insulin production?

A

Circadian rhythm

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14
Q

How many peptides make up insulin?

A

51

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15
Q

What is the structure of active insulin?

A

2 chains: A and B, with inter- and intra-chain disulfide bonds

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16
Q

Why can insulin from different species be used to appropriately signal in diabetic human patients?

A

Sequence and structure highly conserved across species

17
Q

Why can’t insulin be administered orally?

A

Because proteolytically digested in gut

18
Q

What is the structure of the insulin receptor?

A

2 extracellular alpha chains
2 transmembrane beta chains
Disulphide bond linked
Tyrosine kinase domain on beta chains intracellularly

19
Q

What are the target tissues of insulin?

A

Muscle
Adipose tissue
Liver

20
Q

What is the role of the cytosolic domain of the insulin receptor?

A

Signalling

21
Q

What is the affinity and specificity of the insulin receptor for binding insulin?

A

High affinity and specificity

22
Q

What are the two models of how insulin activates its receptor?

A

Model 1: insulin induces change in orientation of receptor transmembrane domain
Model 2: yo-yo model = insulin induces changes in positioning of kinase domains by changing conformation of juxtamembrane segments of beta chain

23
Q

What is the first step after insulin binds to its receptor?

A

Trans-autophosphorylation

- Multiple tyrosine residues phosphorylated in intracellular domains

24
Q

Which domains in proteins recognise phosphorylated tyrosines?

A

SH2

PTB

25
Q

What does the tyrosine phosphorylated insulin receptor bind?

A

Scaffold protein = insulin receptor substrate (IRS)1 via PTB domain

26
Q

What happens when IRS1 binds the tyrosine phosphorylated insulin receptor?

A

Insulin receptor phosphorylates tyrosine residues in IRS1

27
Q

What does tyrosine phosphorylation of IRS1 lead to?

A

Signal diversification - multiple signalling cascades activated

28
Q

What is the impact of insulin on gene expression?

A

Both up- and down-regulates genes

Gives slow but relatively sustained impact

29
Q

What is GSK3?

A

Protein that when active, inactivates glycogen synthase

When inactive, glycogen synthase can be active

30
Q

What is the effect of insulin receptor signalling on GSK3?

A

Inactivates it > activated glycogen synthase

31
Q

What is the impact of non-nuclear changes mediated by insulin receptor signalling?

A

Alters existing proteins > relatively rapid impact

32
Q

How does insulin enhance glucose uptake in muscle and adipose tissue?

A

Changes trafficking of GLUT4 to cell surface > more GLUT4 on surface > more glucose enters cell

33
Q

How can a protein without enzymatic activity; eg: IRS1, contribute to insulin signalling?

A

Acts as signalling scaffold/adaptor protein > diversification of signalling events

MD1 Metabolism (18 decks)

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