Insulin and metabolic reglation\ Flashcards
3 pancreas endocrine cells and what they produce
- B cell - insulin, amylin, c-peptide
- a cell - glucagon
- omega cell - somatostatin
what triggers insulin release
glucose levels
what is the path by which glucose releases insuling in B cell
- glucose in > glycolysis and ATP production
- ATP inhibits K channel (less K out) reducing membrane potential
- membrane depolarization leads to Ca influx
- exocytosis of insulin post-Ca influx
how is insulin synthesized in B-cell
- DNA>mRNA>preproinsulin
- prepro has signal sequence removed and 3 disulfides formed > proinsulin
- proinsuling has c-peptide released and left with insulin
what is timing of insulin after meal (2)
- intial spike of exocytosis
2. slow gain as more is created after
6 stimulators of insulin
- glucose (major)
- AAs
- FFAs
- GLP-1
- glucagon
- Ach
3 inhibitors of insulin
- somatostatin
- insulin
- norepinepherine
how does microRNA inhibit insulin
binds to and inhibits translation of myotrophin mRNA, which is needed for secretion of vesicle
what are insulin’s role in anabolic processes (5)
- recruitment of glucose trnasporters for uptake
- stim glycogen synsthesis and inhib glycogen breakdown
- increase FA synthesis
- upregulate glucokinase
- increase AA uptake and protein synthesis
how does insuling promote gulcose uptake
insulin binding triggers vesicle carryin GLUT4 transporter to go to cell membrane surface
aside from insulin, what else can recruit transporters
exercise
how does insulin signalling work?
- insulin binds to receptor
- tyrosine kinase activated protein kinases
- protetin kinase phosphoryalte other proteins, causing them to signal
how does insulin reverse effects of glucagon and epi
- both glucagon and epi phosphorylate glycogen phosphorylase a, which leads to glycogen breakdown
- insulin activates protein phophotase, which dephosphorylates thise enzyme, inhibiting glycogen breakdown
how does glucose enter the liver
down concentration gradient
how are low intracellular glucose level maintained (3)
- glucose phosphoryalted
- glycogen synthesis
- reduced glycogen breakdown
3 proteins involved
- GLUT2
- glucokinase
- glycogen synthase
what is glucagon released
what gluc. drops below 100mg/dL
how does glucagon prevent hypoglycemia
increases liver glycogenolysis and gluconeogenisis
what is glucagon signalling pathway
GCPRs and phosphorylation cascade
2 other results of glucagon
- beta oxidatiokn
2. ketogenisis
3 possible products of proglucagon and where from/functions
- glucagon - a cells of panc
- GLP-1 - endocrine of small int. - insulin release
- GLP-2 - intestine endocrine - inhibit food intake
what do somatostatins do
inhibit endo and exocrine secretions
how is amylin secreted
from islet with insulin
location and Function of amylin action (3)
- stomach - slows emptying and slows acid secretion
- brain - decreases appetite
- pancreas - decrease glucagon secretions
what is type 1 diabetes
autoimmune destruction of B cells
what must be regulated in type 1 (3)
- insulin
- carb intake
- physical activity
7 risk factors for diabetic hypoglycemia
- bad insulin dosing
- skipped meals of snacks
- reduced dietary carbs
- increased glucose usage (excercise)
- decreased gluconeogenisis (alcohol)
- increased insulin sensititvety
- decreased insulin clearance (renal)
how to treat hypoglycemia
glucose
4 Sx of hyperglycemia
- fluid intake and thisrt
- frequent urination
- high ketones (sweet breath)
- glucosuria
- rapid deep breath (acidosis)
- high blood tonicity (results in K loss)
how does hyperglycemia cause retinal damage
glucose converted to sorbitol
how does hyperglycemia cause ketosis
excess fat breakdown leads to ketones
what happens when not enough glucose in cell
break down fat and protein instead
where does ketogenisis occur
in mitochondira when acetyl CoA levels rise
what are the 3 ketone bodies produced
- acetoacetate
- 3-hydroxybutyrate
- acetone
what are ketone used for
alternative E source by bain, heart and muscle
how does body use ketone bodies as fuel
1 3-hydroxybutyrate converted to 2 actyl CoA
why does citric acid cycle slow without glucose
pyruvate not replensihed
what are consequences of high ketones
drop in blood pH - ketoacidosis
how is ketoacidosis treated
life threatening - bicarb injections
what is path of ketogenisis
- no glucose so FFA are release from adipose
- FFAs undergo B-oxidation in liver
- ketone bodies formed
how does diabetes effect water balance
- high glucose and ketone > hypertonicity
- dehydration due to hypertonicity
- polyuria to get rid of water in blood
- water loss leads to hypotension
- low BP can lead to loss of consciousness
- kidney failure due to excessive processing
