diabetes Flashcards
(18 cards)
daibetes mellitus
chronic elevation in blood glucose levels
type 1 diabetes
juvenile onset
insulin dependent
type 2 diabetes
adult onset
non insulin dependent
initial high insulin secretion, glucotoxicity may lead to beta-cell dysfunction
gestational diabetes
hyperglycaemia for the first time during pregnancy
hormone secretion from the pancreatic islet
beta cells produce insulin to reduce blood glucose
alpha cells produce glucgaon; increase blood glucose
delta cells produce somatostatin; inhibits secretion of other hormones
PP cells produce pancreatic polypeptide; effects of metabolism appetite
***beta cell cellular pathway
glucose enteres on GLUT2 receptor
increases ATP
causes K channels to close , and decreases intracellular potassium
membrane depolarisation
calcium influx and increase in intracellular calcium
release of insulin
synthesis of insulin
insulin mRNA translated as a single chain pre cursor - PREPROINSULIN
preproinsulin directed to rough ER and signal peptide cleaved to generate PROINSULIN
proinsulin travels to golgi and enters immature secretory vesicles cleaved to generate mature INSULIN and C PEPTIDE
insuulin (peptide chains A and B) + C peptide stored in secretory granules
why do you assess beta cell function using C-peptide?
it is more stable in blood stream than insulin
insulin stimulated glucose uptake
insulin uptake
signalling cascade
GLUT4 translocation to membrane and entry of glucose
natural history of type 1 diabetes
genetic predisposition
loss of beta cells have relapsing events and body tries to componsate and so not a linear decline
2 or more islet antibodies
no C-peptide present
pathophysiology of type 2 diabetes
cells are resistant to insulin
adaption of beta cells, so beta cell mass increases, becomes more resistant and insulin levels increase, beta cells decrease and glucose increases
classic drugs of diabetes
target insulin related pathways
DPP4 inhibitors, GLP-1 antagonists, insulin
non classical drugs of diabetes
target other pathways
SGLT2 targets kidneys
SGLT2
targets kidneys to lower blood glucose levels
all of the glucose is filtered through at the glomerulus, but then ends up back in bloodstream due to reabsorption, so no glucose ends up in the collecting duct and urine
majority of reabsorption- 90%
on apical membrane
sodium gradient pumps sodium out to the blood, allowing sodium to come in basal side. glucose comes in
Glut-2 glucose exits cell and enteres blood stream
SGLT1
down stream of SGLT2
takes up remaining glucose
SGLT2 transporters in diabetes
get saturated
all glucose gets filtered
not all glucose gets reabsorbed and ends up in the urine
MOA of SGLT2 antagonists
promotes glucose excretion into urine
independent of severity of insulin resistance and beta cell function
SGLT1 upregulates to compensate for that, therefore don’t completely block glucose reabsorption, target both transportes for greater effect
current target for diabetic kidney disease
ACE inhibitors
angiotensin receptor blockers
blood pressure lowering effect, puts less pressure through the kidneys
