PBL 1 : T1DM Flashcards
What is the Islet of Langerhans and what does it secrete?
Cluster of endocrine cells in the pancreas which secrete endocrine hormones
what do alpha cells secrete? where are they found? and how much secretion do they contribute ?
Glucagon
Found around outer edge
around 20%
What cells secrete insulin? Where are they found in the islet of Langerhans? how much secretion do they contribute?
Beta cells
Found in the middle
about 70%
what do delta cells secrete? how much secretion do they contribute ?
what do PP cells secrete and how much secretion do they contribute
Somatostatin
About 10%
secretes pancreatic polypeptide (2%)
What is insulin? Describe what it is made up of
Insulin is a polypeptide hormone
It consists of 2 short chains- alpha and beta linked by disulphide bonds
Describe the steps int he synthesis of insulin
Insulin is synthesised as a pro-hormone:
Insulin mRNA is translated as a single chain precursor called Preproinsulin
Signal sequence is cleaved off to generate Proinsulin
Endopeptidases cleave off the C-peptide to generate mature form of Insulin
what is also packaged into granules along with insulin?
C peptide
Describe the process of insulin release in response to post-prandial rise in glucose
1) Glucose enters the beta cells via GLUT2 transporter through facilitated diffusion
2) Glucose is then phosphorylated by glucokinase to generate glucose-6-phosphate, which is then metabolised via oxidative phosphorylation to produce ATP
3) Elevated ATP levels cause the ATP-dependant K+ channels to close, resulting in depolarisation (inside cell becomes more +ve since no K+ leaving)
4) Influx of Ca2+ ions into the cell via voltage-gates Ca channels
5) Ca2+ entry stimulates the vesicles containing insulin to fuse with plasma membrane and release insulin into the extracellular fluid by exocytosis.
which chemicals/factors stimulate insulin secretion?
Amino acids e.g. arginine and leucine Parasympathetic innervation sulfonylurea gastrointestinal tract peptides e.g. cholecystokinin Incretins
which chemicals/factors inhibit insulin secretion?
noradrenaline
sympathetic innervation
somatostatin
what happens to remaining insulin which is not taken up by receptors on target cells?
remaining insulin is degraded by the enzyme insulinase
where are insulin receptors primarily found?
found on most tissues but primarily located in the liver, striated muscle and adipocytes
Describe the binding of insulin to insulin receptors
The receptor is a tyrosine kinase which is made of 2 alpha and 2 beta units and phosphorylates itself.
When insulin binds to the extracellular alpha subunits, the beta subunits become activated and undergo a conformational change.
The Beta-subunit receptors auto phosphorylate themselves on tyrosine residues.
Receptor tyrosine kinase activity begins an intercellular cascade of phosphorylation:
o The phosphorylated receptor forms a complex with and phosphorylates Insulin Receptor Substrate-1 (IRS)
(cascade of phosphorylation occurs)
Eventually, this leads to translocation of GLUT4 transporters
is insulin an anabolic or catabolic hormone?
anabolic
Describe the actions of insulin - what it stimulates and inhibits
Stimulates:
• Glucose uptake (Muscle, adipocytes)
• Glycogen synthesis – (Muscle, liver)
• Fatty acid synthesis – glucose storage in form of lipids (Liver, adipocytes
Inhibits:
• Lipolysis – breakdown of lipids (adipose tissue)
• Gluconeogenesis – production of glucose from non-carbohydrate source
is glucagon an anabolic or catabolic hormone?
Catabolic hormone
describe the synthesis of glucagon and where it occurs
Glucagon is synthesised as preproglucagon which is proteolytically cleaved in the alpha cell to produce proglucagon and then glucagon.
