3 Insulin Secretion And Signalling Flashcards
What is the cause and management of persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI)?
Cause : k+ ATP channel mutations (closed)
Management : diazoxide or surgery to open channel
What disease does glucokinase mutations cause?
Maturity onset diabetes of the young
What is the definition of pleiotrophy?
Occurs when one gene influences multiple, unrelated phenotypic traits
What effects does insulin have on it’s target tissues to fuel homeostasis?
- 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
How does insulin act as a growth factor?
- increases amino acid uptake
- promotes transcription and translation
- affects gene transcription of some genes
- protects from apoptosis
What are some cellular effects induced by insulin?
- 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
Which kinase family does insulin belong to?
Receptor tyrosine kinase family
Phosphorylated specific tyrosines on themselves and other intracellular signalling proteins
What are some subfamilies of receptor tyrosine kinases?
What domains do they consist of?
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
Explain the mechanism of normal RTK activation?
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
What is the insulin receptor composed of?
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
What nutrients stimulate insulin secretion. How?
Glucose and leucine and arginine
Membrane depolarisation and calcium signal
What neurotransmitter a promote insulin secretion
Acetylcholine
What factors inhibit insulin secretion
Adrenaline, epinephrine, noradrenaline, norepinephrine by inhibition of AC/cAMP
What are th pe steps of stimulation of insulin secretion in response to rise in blood glucose
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
Which pancreatic exocrine cells secrete substances into the digestive tract?
Acinar and duct cells
What endocrine cells are arranged within pancreatic exocrine tissues?
Islets of Langerhans
What us Kir channel fully called?
Inwardly rectifying potassium sensitive channel
What are the cells within the islets of langerhans and what do they secrete?
F endocrine cells: Secrete pancreatic polypeptide
Delta cells: Secrete somatostatin
Beta cells: Secrete insulin
Alpha cells: Secrete glucagon
How do hormones enter and exit the glomerular-like capillary network in the pancreas?
Enter through afferent arterioles (carrying information such as nutrient levels)
Exit through efferent arterioles (carrying insulin)
What causes maturity onset diabetes of the young? (MODY)
Glucokinase mutations
What causes Persistant hyperinsulanaemic hypoglycemia of infancy (PHHI) and what drug is used to manage it?
K+/ATP channel mutations
Managed by Diazoxide
Describe the cAMP second messenger system
Regulation of adenylate cyclase by the activation of trimeric G-protein by G protein receptor
Signal->Trimeric G protein -> Adenyl cyclase -> cAMP -> cAMP kinase
Describe the phosphatidylinositol second messenger system
Activation of phospholipase C through a receptor linked to trimeric G proteins
Ligand -> Trimeric G protein -> (GTP->GDP) -> Phospholipase C -> InsP3 + DAG
Which glucose channel triggers release of insulin?
GLUT 2 only
