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REGUB 10: glucagon + other diabetogenic hormones (metabolic effects of…
REGUB 10: glucagon + other diabetogenic hormones
glucagon structure + synthesis
polypeptide (29 AAs)
synthesised as large precursor (proglucagon)
proteolytically cleaved
made in alpha pancreatic islets in response to low blood glucose
short T1/2 (5mins)
stimulating factors = low blood glucose, protein rich meal (high AA conc inhibits insulin), NA/adrenaline (anticipating increased glucose use)
inhibiting factors = high blood glucose, insulin (paracrine)
metabolic effects of glucagon
raises blood glucose
prevents hypoglycaemia
promotes FA oxidation, forming ketone bodies
increases liver AA uptake for gluconeogenesis
promotes glycogenolysis, inhibits glycogenesis
MOA: @ GPCRs - adenylate cyclase - cAMP - PKA phosphorylation
increases activity of...
glycogen phosphorylase (glycogen -> G1P)
G6 phosphatase (G6P -> glucose)
Fructose 1,6 bisphosphatase (F1,6 bisP -> F6P)
PEP carboxykinase + transaminases (gluconeogenesis)
decreases activity of...
glycogen synthase (glycogenesis)
phosphofructokinase + pyruvate kinase (glycolysis)
AcoA carboylase + HMGcoA reductase (FA + chol synthesis)
hypoglycaemia
symptoms = Whipple's triad...
1) CNS effects
adrenergic: anxiety, tremor, swear
neuroglycopenic: confusion, slurred speech, seizures, coma
2) blood glucose < 40 mg/dL
3) Symptoms resolve after glucose admin
how does body respond?
pancreas makes more glucagon, less insulin
low blood glucose sensed by hypothal + stimulates adrenaline, cortisol, GH
hypoglycaemia subtypes
insulin-induced
poorly controlled type 1 diabetes
treat with oral glucose or IM injection (if unconscious)
postprandial
excessive insulin release after a meal
transcient
mild adrenergic symptoms
eat small portions more frequently
fasting
neuroglycopenic symptoms
rare, can indicate serious underlying issue
anorexia nervosa, pancreas tumor, adrenal insufficiency, liver damage
alcohol induced
excess NADH - diverts private + OAA away from gluconeogenesis
esp when person takes irregular/infrequent meals (depleted glycogen stores)