Hormone Signalling Pathways Flashcards

Question

What is the signal for insulin release? (pathway) 1st step that needs to happen for insulin to be secreted? what happens once its in the beta cells? what's the signal that helps inhibit the potassium ATP channel? what then causes the insulin granules to be secreted?

Answer 1

glucose is taken up into the cell by GLUT2 of the beta cells via Facilitated Diffusion it'll enter the glycolytic pathway and converted to G6P through glucokinase. then glycolysis, TCA, and the glucose has generated ATP! so you have elevated ATP and that inhibits a potassium ATP channel. this causes depolarization of the plasma membrane that spreads across until it reaches a Ca2+ channel! lots of calcium enters the cell, extra calcium comes in and causes insulin granules to be mobilized and released into the blood stream!

Answer 2

they use the potassium channel as their target in diabetes type 2, glucose isn't up taking as well, so medicine targets at the level of the potassium channel to increase ca2+ --> secrete more insulin to uptake glucose!

Answer 3

insulin from the pancreatic beta cells gets to the target cell RTK. insulin binds to the RTK (doesn't really dimerize since insulin is a dimer already). in response to binding, there's a phosphorylation of the tyrosine in the intracellular domains. recruitment of IRS-1 (insulin receptor substrate) recruits GRB-2 after IRS-1 comes. once recruited, it turns on the RAS or MAPK pathway. the RAS phosphorylates several proteins which increase glucokinase transcription (which increases glucose utilization) in the other way IRS-1 increases PI-3-kinase which activates PKB which phosphorylates stuff increases messages to GLUT4 and more gets inserted to the plasma membrane of the target cells and glucose comes in, and it activates glycogen synthase.

Answer 4

increase glucose uptake, increase glycogen synthesis | increase glucose utilization (through glucokinase)!

Answer 5

the receptor becomes internalized by the target cell. it can be degraded by proteases OR recycled back to the plasma membrane and do it again.. Insulin down regulates its own receptor by decreasing the rate of synthesis or degradation.

Answer 6

failure of normal amounts of insulin to elicit expected response. you've given the person enough insulin and glucose but the glucose isn't cleared from the body.

Answer 7

down regulation of the insulin receptor (RTK) defects in the insulin receptor (75 mutations found thus far) Defects in Signaling Defects in IRS1 and IRS2 (insulin signaling) --> phosphorylating serine instead of tyrosine (via Ser/Thr kinase) inhibits downstream stuff... this inactivates IRS1 and 2. this same process also actually inhibits PKB so you're not going to have all the stuff that we have on that right arm path. ser/thr kinase is the enzyme doing all this... this is activated by cytokines, free fatty acids, DAG, ceramics, inflammatory molecules this is a precursor for type 2 diabetes because the body compensates by trying to make more insulin, the receptor isn't working, so things go really bad. REMEMBER: insulin downregulates its own receptor.

Answer 8

work as transcription factors for lipophilic signaling. they're named based on the ligand that binds to them. we don't know what the ligands are... unknown ligands. (discovered by DNA sequencing) VERY IMPORTANT DRUG TARGETS

Answer 9

all NRs have the basic structure with 3 major domains! Ligand Binding domain DNA binding Domain "Activation function domain or Transcription Activating domain" when it's inactive, it's surrounded by inhibitory proteins. --> keep it inactive when the ligand binds to the ligand binding domain, it undergoes massive conformational changes... then all of the inhibitory proteins are dissociated and coactivators are bound to the ligand binding domain and the transcription activating domain. this change allows it to bind to the DNA and serve as a transcription factor --> undergoes transcription and increase or decrease mRNA production.

Answer 10

DNA-binding domain. found on pretty much all nuclear domain (HRE regions)

Answer 11

hormone binding to its receptor and a set of proteins are generated initially... or the primary-response proteins. primary-response proteins that are generated shut off the primary response and turn on the secondary response! testosterone increases spermatogenesis (primary) but builds secondary sex characteristics (body hair, puberty). the secondary response takes years to response (hence the delayed)

Answer 12

(works through the nuclear receptor) alpha and beta.. both of which are made by product of different genes. alpha is present abundantly in uterus, vagina, ovaries beta in ovaries, prostate but also lung brain, bone, vasculature. some cells have both! for the estrogen receptor to work they need to dimerize (a + a), (b + b), or (a + b)

Answer 13

nuclear receptor so 3 domains estrogen binds to estrogen receptor --> dimerizes the receptor ==> binds to estrogen response element on the DNA --> recruits coactivators --> promotes the action of HISTONE ACETYL TRANSFERASE (HAT)! Hat loosens up the chromatin and allows transcription to occur!

Answer 14

treats breast cancer! antagonizes estrogen. it binds to the same receptor but activates a different pathway that results in inhibiting transcription of estrogen. so it is metabolized by the liver by cytochrome P450 to 4-hydroxy-tamoxifen --> binds to same receptor, dimerizes it --> recruits HISTONE DEACETYLASE instead.. this makes the chromatin super dense and prevents transcription

Answer 15

we think it's in the nucleus but there are some studies that show it's in the cytoplasm... some even say there's evidence on the cytoplasm. so some say it's "non-genomic".. but primary evidence is it's a nuclear receptor.

Answer 16

Beta cells of the pancreas Liver, skeletal muscle, adipocytes, brain