case 6 - insulin and glucagon Flashcards
where is insulin produced
by the beta cells in the pancreas
what is insulin responsible for
for regulating the movement of glucose from the blood into the cells
how is it released into the bloodstream
in an endocrine fashion
what is the structure of insulin
consists of two polypeptide chains, an A chain and a B chain, covalently linked by two inter-chain disulfide bridges. there is a third, intra-chain disulfide bridge
what is the first step in the synthesis of insulin
the insulin mRNA is translated as a single chain precursor called preproinsulin. there is then removal of its signal peptide at the N-terminus during insertion at the endoplasmic reticulum
what does this generate
proinsulin
what happens in the endoplasmic reticulum
the endopeptidases excise a connecting peptide (C - peptide) between the A and B chains. this breaks the single chain into two strands that are help together by disulfide bridgess.
what does this generate
the mature form of insulin
what happens to the eqimolar amounts of insulin and free c-peptide
they are packaged in the golgi apparatus into storage vesicles which accumulate in the cytoplasm
what is the stimulation for insulin release
a rise in glucose levels in the extra cellular fluid
glucose is transported into the beta cells via what channels
by facilitated diffusion through GLUT2 channels
what does a rise in glucose concentration in ECF cause
causes a rise in glucose concentration in beta cells.
what does this lead to
this leads to membrane depolarisation of ATP sensitive K+ channels, opening Ca2+ channels
what does this trigger
an influx of calcium
what is the two stage process by which an increase in intracellular Ca2+ triggers insulin release
Margination: the process by which insulin storage vesicles move to the cell surface.
Exocytosis: This is fusion of the vesicle membrane with the plasma membrane, with release of the vesicle’s entire contents
what are the 2 phases of insulin secretion
Pulsatile release (rapid onset): Short term blood glucose control: clearing absorbed nutrients from the blood following a meal.
Protracted release (longer): Long term insulin release for glucose uptake e.g. for cell growth, cell division, stimulating protein synthesis and DNA replication.
what does insulin bind to
a highly specific insulin receptor on cell surfaces
the receptor is a dimer
what 2 subunits is the insulin receptor made up of
one alpha chain - exterior of cell membrane
one beta chain - spans cell membrane in a single segment
what are these two chains connected by
a single disulphide bond
what happens once insulin is detected
the alpha chains move together and fold around the insulin
what does this do
this moves the beta chains together making them an active tyrosine kinase
what does the active tyrosine kinase initiate
initiates a phosphorylation cascade which results in an increase of GLUT4 expression - a protein channel to allow glucose uptake. the result is an increase in glucose uptake by cells
overall, what can insulin be considered as
the anabolic or building hormone - it assists processes that build compounds for storage and decrease processes that break down those storage reserves
what stimulates insulin secretion
GI tract hormones
acetylcholiine
what inhibits insulin secretion
adrenaline
noradrenaline
what is glucagon
the hormone that opposes insulin, so it acts to raise blood glucose levels
what is it produced by and what kind of hormone is it
it is a peptide hormone, produced by the alpha cells of the pancreas
what is the structure of glucagon
a single chain polypeptide and has no disulphide bridges, making it incredibly flexible
what is the synthesis of glucagon
a precursor molecule, proglucagon, undergoes post-translational processing to become a biologically active glucagon
how is glucagon secreted
secreted by alpha cells in the islets of Langerhans in the tail of the pancreas.
what is detected by alpha cells and what does this lead to
low glucose levels in the blood are detected by alpha cells, stimulating the release of glucagon.
Like insulin, this undergoes margination and exocytosis to be released.
what is the mechanism of action of glucagon
glucagon binds to a specific receptor in the membrane, a G protein coupled receptor
what does this activate
this activates adenylate cyclase which increases cAMP intracellularly.
what does this increase in cAMP lead to
activates protein kinase A, which phosphorylates and activates a number of important enzymes in target cell
what are the overall affects of glucagon
Increased glycogenolysis
Decreased glycogenesis
Increased gluconeogenesis
Increased ketogenesis
It also increases lipolysis in adipose tissue.
what stimulates glucagon secretion
adrenaline
noradrenaline
what inhibits glucagon secretion
GI tract hormones
acetylcholine
