diabetes

Question 1

daibetes mellitus

Answer 1

chronic elevation in blood glucose levels

Question 2

type 1 diabetes

Answer 2

juvenile onset

insulin dependent

Question 3

type 2 diabetes

Answer 3

adult onset
non insulin dependent
initial high insulin secretion, glucotoxicity may lead to beta-cell dysfunction

Question 4

gestational diabetes

Answer 4

hyperglycaemia for the first time during pregnancy

Question 5

hormone secretion from the pancreatic islet

Answer 5

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

Question 6

***beta cell cellular pathway

Answer 6

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

Question 7

synthesis of insulin

Answer 7

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

Question 8

why do you assess beta cell function using C-peptide?

Answer 8

it is more stable in blood stream than insulin

Question 9

insulin stimulated glucose uptake

Answer 9

insulin uptake

signalling cascade

GLUT4 translocation to membrane and entry of glucose

Question 10

natural history of type 1 diabetes

Answer 10

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

Question 11

pathophysiology of type 2 diabetes

Answer 11

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

Question 12

classic drugs of diabetes

Answer 12

target insulin related pathways

DPP4 inhibitors, GLP-1 antagonists, insulin

Question 13

non classical drugs of diabetes

Answer 13

target other pathways

SGLT2 targets kidneys

Question 14

SGLT2

Answer 14

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

Question 15

SGLT1

Answer 15

down stream of SGLT2

takes up remaining glucose

Question 16

SGLT2 transporters in diabetes

Answer 16

get saturated
all glucose gets filtered
not all glucose gets reabsorbed and ends up in the urine

Question 17

MOA of SGLT2 antagonists

Answer 17

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

Question 18

current target for diabetic kidney disease

Answer 18

ACE inhibitors
angiotensin receptor blockers

blood pressure lowering effect, puts less pressure through the kidneys