Lecture 4 - Signal Transduction in regulating Homeostasis and the consequences of Defects

What is hypoglycaemia?

abnormally low blood glucose

What is hyperglycaemia?

abnormally high blood glucose

Which three hormones regulate blood glucose?

glucagon, epinephrine and insulin

What is the effect of glucagon, epinephrine and insulin on blood glucose?

glucagon and epinephrine increase, insulin decreases

Where is glucagon produced?

alpha cells of pancreas

Where is epinephrine produced?

adrenal glands

When is epinephrine released?

during stress or exercise, fight or flight

What type of receptor do glucagon and epinephrine use?

gpcrs

Which G protein is activated by glucagon and epinephrine?

gs protein

What enzyme is activated by Gs?

adenylate cyclase

What does adenylate cyclase produce?

camp from atp

What does cAMP activate?

protein kinase a

What does PKA activate in the glycogen breakdown pathway?

phosphorylase kinase through phosphorylation

What does phosphorylase kinase activate?

glycogen phosphorylase

What does glycogen phosphorylase do?

breaks down glycogen into glucose-1-phosphate

What is the complete glucagon and epinephrine signalling pathway?

gpcr, gs, adenylate cyclase, camp, pka, phosphorylase kinase, glycogen phosphorylase, glycogen breakdown

What are the three effects of glucagon on the liver?

increase glycogen breakdown, increase gluconeogenesis, decrease glycolysis

What is gluconeogenesis?

production of new glucose

What is glycogen breakdown?

breaking stored glycogen into glucose 1 phosphate

What is glycolysis?

breaking down glucose to produce energy

What is the main function of epinephrine during stress or exercise?

increase glycogen breakdown and promotes energy availability

What is phosphorylation?

adding phosphate group to protein, activates or deactivates it

What is dephosphorylation?

removing phosphate group from a protein

How is glycogen breakdown switched off?

hormone stimulation stops, gs hydrolyses gtp to gdp, pde breaks down camp into amp, protein phosphates remove phosphate groups from enzymes

Where is insulin produced?

beta cells of pancreas

What type of receptor does insulin use?

receptor tyrosine kinase

What are the two main subunits of the insulin receptor?

alpha and beta subunits

Where does insulin bind on its receptor?

extracellular alpha subunits

What is autophosphorylation?

activated receptor adds phosphate group to itself

What is IRS-1?

insulin receptor substrate-1

What enzyme is activated by IRS-1?

phosphoinositide 3-kinase

What does PI3K do?

converts pip2 into pip3

What activates Akt in the insulin signalling pathway?

pdk1 phosphorylates and activates akt

What is the complete insulin signalling pathway?

insulin, rtk, autophosphorylation, irs-1, p13k, pip3, pdk1, akt

What are the two main effects of insulin on carbohydrate metabolism?

increases glucose uptake into muscle cells, increases glycogen synthesis in liver

How does insulin regulate glucagon release?

insulin inhibits glucagon release and stimulates somatostatin secretion, which inhibits glucagon

What causes Type I diabetes?

destruction of beta cells, little or no insulin production

What happens to blood glucose in Type I diabetes?

blood glucose increases because normal insulin regulation lost

How is insulin used to treat diabetes?

insulin medication binds to insulin receptors to regulate blood glucose

What is the function of the MC4 receptor?

regulates appetite and energy balance

What can mutations in the MC4 receptor cause?

extreme obesity

What is the effect of cholera toxin on Gs?

locks gs alpha subunit in its active form

What happens to adenylate cyclase when Gs remains active?

remains continuously activated, causing abnormally high camp levels

How does cholera cause diarrhoea?

increased camp disrupts ion and water regulation in intestinal cells, causing excessive water and electrolyte loss

How is cholera treated?

rehydration using oral rehydration solution