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Endo and cell signalling > 3 Insulin Secretion And Signalling > Flashcards

3 Insulin Secretion And Signalling Flashcards

0
Q

What is the cause and management of persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI)?

A

Cause : k+ ATP channel mutations (closed)

Management : diazoxide or surgery to open channel

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1
Q

What disease does glucokinase mutations cause?

A

Maturity onset diabetes of the young

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2
Q

What is the definition of pleiotrophy?

A

Occurs when one gene influences multiple, unrelated phenotypic traits

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3
Q

What effects does insulin have on it’s target tissues to fuel homeostasis?

A
  • promotes glucose uptake
  • promotes conversion of glucose to glycogen in liver and muscle
  • increases Fa synthesis from acetyl CoA
  • inhibits lipolysis
  • inhibits glycogenolysis
  • inhibits gluconeogenesis
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4
Q

How does insulin act as a growth factor?

A
  • increases amino acid uptake
  • promotes transcription and translation
  • affects gene transcription of some genes
  • protects from apoptosis
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5
Q

What are some cellular effects induced by insulin?

A
  • phosphorylation of insulin receptor substrates
  • activation of PtdIns3 kinase
  • activation of Ras
  • phosphorylation of kinases and phosphates
  • phosphorylation or dephosphorylation of metabolic enzymes
  • GLUT4 translocation
  • regulation of gene expression
  • modulation of protein synth
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6
Q

Which kinase family does insulin belong to?

A

Receptor tyrosine kinase family

Phosphorylated specific tyrosines on themselves and other intracellular signalling proteins

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7
Q

What are some subfamilies of receptor tyrosine kinases?

What domains do they consist of?

A

EGF receptor, IGF1 receptor, NGF receptor, PDGF coupled with MCSF receptor, FGF receptor, VEGF receptor, Eph receptor

They consist of cysteine rich domain and tyrosine kinase domain

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8
Q

Explain the mechanism of normal RTK activation?

A

Ligand binding causes the receptor to dimerise
Brings the two receptor chains together
Kinase domains become active and phosphorylate - transautoohosphorylation
Phosphorylated tyrosines serve as docking sites for intracellular signal proteins, sending a relay signal downstream

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9
Q

What is the insulin receptor composed of?

A

Two alpha subunits and two beta subunits linked by disulfide bonds

The two beta subunits penetrate through the plasma membrane and contain ATP binding and tyrosine kinase domains

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10
Q

What nutrients stimulate insulin secretion. How?

A

Glucose and leucine and arginine

Membrane depolarisation and calcium signal

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11
Q

What neurotransmitter a promote insulin secretion

A

Acetylcholine

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12
Q

What factors inhibit insulin secretion

A

Adrenaline, epinephrine, noradrenaline, norepinephrine by inhibition of AC/cAMP

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13
Q

What are th pe steps of stimulation of insulin secretion in response to rise in blood glucose

A

Entry of glucose in GLUT2
Metabolism of glucose
Binding of ATP to KAtP channels to inhibit channel - membrane depolarisation
Opens calcium channels triggering insulin exocytosis

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14
Q

Which pancreatic exocrine cells secrete substances into the digestive tract?

A

Acinar and duct cells

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15
Q

What endocrine cells are arranged within pancreatic exocrine tissues?

A

Islets of Langerhans

16
Q

What us Kir channel fully called?

A

Inwardly rectifying potassium sensitive channel

17
Q

What are the cells within the islets of langerhans and what do they secrete?

A

F endocrine cells: Secrete pancreatic polypeptide
Delta cells: Secrete somatostatin
Beta cells: Secrete insulin
Alpha cells: Secrete glucagon

18
Q

How do hormones enter and exit the glomerular-like capillary network in the pancreas?

A

Enter through afferent arterioles (carrying information such as nutrient levels)
Exit through efferent arterioles (carrying insulin)

19
Q

What causes maturity onset diabetes of the young? (MODY)

A

Glucokinase mutations

20
Q

What causes Persistant hyperinsulanaemic hypoglycemia of infancy (PHHI) and what drug is used to manage it?

A

K+/ATP channel mutations

Managed by Diazoxide

21
Q

Describe the cAMP second messenger system

A

Regulation of adenylate cyclase by the activation of trimeric G-protein by G protein receptor

Signal->Trimeric G protein -> Adenyl cyclase -> cAMP -> cAMP kinase

22
Q

Describe the phosphatidylinositol second messenger system

A

Activation of phospholipase C through a receptor linked to trimeric G proteins

Ligand -> Trimeric G protein -> (GTP->GDP) -> Phospholipase C -> InsP3 + DAG

23
Q

Which glucose channel triggers release of insulin?

A

GLUT 2 only

Endo and cell signalling (12 decks)

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