Acute regulation of glucose Flashcards
after a meal what level can portal glucose increase to
20 mM
what types of cells secrete glucagon and insulin
insulin B cells in the islets of lengerhams
glucagon alpha cells
describe the structure of islets of langerhams between b and a cells
b cells mainly central and most abundant
a cells at the periphery
what are the third type of cells in the islet of langerham
delta which produce somatostatin and a few f cells which produce pancreatic polypeptide
how do b cells produce insulin
sense glucose and aa in the blood by using it to make ATP
entry of glucose via glut2 is insulin sensitive and low affinity
atp closes Katp channels depolarising the membrane
Ca influx and CICR induce exocytosis of insulin
which method of ingesting glucose causes biggest change in insulin
oral rather than iv produces more insulin
describe how the nervous system affects insulin production
PNS drives and SNS inhibits secretion
how do incretins affect insulin
act via cAMP to increases exocytosis
describe the packaging and release of insulin
preprohormone from cells and cleaved to pro hormone
internal disulphide bonds fold up
cleaved in golgi to make A and B chains which are linked
C chain used as biomarker
describe the insulin receptor structure
a receptor tyrosine kinase - the receptor itself is an enzyme
the TK domains phosphorylate each other and nearby proteins in particular a family of insulin receptor substrates
what are the two main pathways of insulin receptor signalling and what are they both mediated by
PI3K and PKB pohorylate proteins altering activity (and inserting GLUT4)
MAPK pathway alters gene expression
both mediated by insulin receptor substrates
what are the effects of insulin on the liver
glycogen storage and VLDL production increase while gluconeogenesis and ketone body production are inhibited
there is no GLUT4 in the liver
what are the effects of insulin on the muscle
GLUT4 inserted and favours use of glucose
glycogen, triglyceride and protein synthesis increase
how does exercise affect insulin on the muscles
via adrenaline also induces GLLUT4 and synergises with insulin
what are the effects of insulin on fat
GLUT 4 inserted and favours uptake of glucose
Triglyceride storage increased
export of FFA and glycerol is reduced
LPL exported to endothelium where is extracts FFA from VLDL
what is glucagon release driven by inhibited by
amino acids and antagonised by glucose
what are the effects of glucagon on the liver
glucagon is a GPCR receptor and linked to Gs
glycogen breakdown and gluconeogenesis increases
presence of G6Pase allows glucose export
fatty acids used as an energy source and for ketone body production
what are the effects of glucagon on fat and muscle
high levels of glucagon causes lipolysis in adipocytes nd proteolysis releasing AA for gluconeogenesis in muscle
when is it common to see high levels on glucagon in the blood
pathologically during ketoacidosis and sepsis and glucagon normally cleared by the liver
what is the structure and function of somatostatin
peptide hormone - mostly 28aa in gut
released from D cells of stomach duodenum and pancreas
acts in paracrine - stimulated by lumen H+ and inhibited by ACh
acts on G cells to inhibit the release of gastrin
inhibits release of CCK and secretin as insulin and glucagon if it can get into the cells
how does exercise affect blood glucose
adrenaline signals via cAMP to enhance glucose production in liver via cori cycle
glycogen breakdown in muscle and GLUT4 insertion via intrinsic AMPK
fatty acid release from adipocytes
what is diabetes mellitus
failure of insulin action leads to high plasma glucose which is lost in urine taking water with it
what are the symptoms of DM
polyuria
polydipsia
weight loss blurred vision
ketoacidosis in type 1
what is DM type 1 causes and effects
primary defect in ability to produce enough insulin
autoimmune disease and B cells destroyed
excess glucagon leads to lipolysis and proteolysis and glluconeogenesis and ketogenesis in the liver
