Insulin and diabetes Flashcards
islets make up how much of what
2% mass of pancrease
size of islets
~100 micro meters
what innervation do islets receive
sympathetic - adrenergic
parasympatheic - cholinergic
types of islet cells
- beta cells secrete insulin (60-80%)
- alpha cells secrete glucagon
- delta cells secrete somatostatin
- PP cells secrete pancreatic polypeptides
where is glucagon secreted from
alpha cells of islets
where is somatostatin secreted from
delta cells of islets
where are beta cells expressed
core of islet
where are alpha cells expressed
outside of islet / periphery
somatostatin inhibits
insulin & glucagon
insulin inhibits
glucagon & somatostatin
glucagon stimulates
insulin and somatostatin release
summary of insulin biosynthesis
nucleus: preproinsulin mRNA is transcribed
ER: preproinsulin mRNA is translated then rapidly cleaved to proinsulin
Golgi: proinulsin packaged to secretory granules
Secretory granules: proinsulin converted to insulin and c-peptide by peptidases
proinuslin structure
- short a chain 21 aa
- longer b chain 30 aa
- c-peptide
connected wih 2 disulphide bonds
how does insulin circulate
mature insulin has low solubilty and forms crystals with Zn2+.
secretory granules fuse with plasma membrane and insulin then circulates blood as a monomer
what is the precursor peptide of insulin
proinsulin; inactive
basal level of insulin
0.4 microgram/ml in the unfed state
7mM
half life of circulating insulin
~5 minutes
where is insulin degraded
mostly in the liver
autoimmune destrcution of iselt beta cells causes
T1DM
what do islets show in T1DM
lymphocyte filatration AKA insulitus
treatments for T1DM
Insulin administration,
human islet transplantation
% of diabates cases that are T1DM
10%
% of diabetes cases that are T2DM
90%
pathology of T2DM
- insulin resistance in peripheral tissues
- beta cell dysfunction causing impaired insulin secretion
uncommon form of diabetes
maturity onsent diabetes of the young - 1-2%
common features of MODY
not overweight and not insulin resistance
causes of MODY
single gene mutations of:
- glucokinase
- transcription factors
mutations cause beta cells defectd leading to insufficient insulin secretion and or synthesis
treatment of MODY
Sulphonylureas