(endo) glucose homeostasis Flashcards
what blood glucose concentration classifies as hypoglycaemia?
when blood glucose levels fall below 4-5 mmol/L
= hypoglycaemia
= cerebral function increasingly impaired
what happens if blood glucose levels are <2 mmol/L?
coma & untimely death can result
why is persistent hyperglycaemia bad?
can result in diabetes mellitus
which hormones act to increase blood glucose levels?
glucagon
cortisol
GH
catecholamines
which hormones act to decrease blood glucose levels?
insulin
what are the phenotypes of diabetes mellitus?
1) type 1 diabetes mellitus
2) type 2 diabetes mellitus
3) maturity-onset diabetes of the young (MODY)
what two types of cells are found in the pancreas?
1) exocrine acinar cells (98%)
2) islets of Langerhans (2%)
name the islet cells of the pancreas
1) alpha cells (glucagon)
2) beta cells (insulin)
3) delta cells (somatostatin)
what type of intercellular communication occurs between islet cells in the pancreas?
paracrine communication
how is paracrine communication enabled between islet cells of the pancreas?
via
1) gap junctions = allow small molecules to pass bw cells directly
2) tight junctions = create small intercellular spaces
what do alpha islet cells of the pancreas secrete?
glucagon
what do beta islet cells of the pancreas secrete?
insulin
what do gamma islet cells of the pancreas secrete?
somatostatin
what is the function of insulin?
1) reduce blood glucose
2) stimulate growth and development
what is the function of glucagon?
increases blood glucose levels
how does the body respond primarily to an increased blood glucose level?
increased blood glucose
= increased stimulation of pancreatic beta cells
= increased insulin secretion
besides an increased blood glucose level, what also stimulates insulin secretion from beta cells?
1) some amino acids, GI hormones
2) SNS activity (via beta pathways)
3) PNS activity
4) glucagon from pancreatic alpha cells
what inhibits insulin secretion from beta cells?
1) SNS activity (via alpha pathways)
2) somatostatin from pancreatic delta cells
how does insulin act to reduce blood glucose levels?
1) increased glycogenesis, glycolysis and increased uptake of glucose via GLUT4 receptors
2) increased amino acid transport, increased protein synthesis
3) increased lipogenesis (reduced lipolysis)
how does the body respond primarily to an reduced blood glucose level?
reduced blood glucose levels
= increased stimulation of alpha cells
= increased glucagon secretion
besides a reduced blood glucose level, what also stimulates glucagon secretion from alpha cells?
1) some amino acids, GI hormones
2) SNS activity (via alpha pathways)
3) PNS activity
what inhibits glucagon secretion from alpha cells?
1) insulin from pancreatic beta cells
2) somatostatin from pancreatic delta cells
how does glucagon act to reduce blood glucose levels?
1) increased hepatic glycogenolysis
2) increased proteolysis and amino acid transport to the liver = gluconeogenesis
3) increased lipolysis = gluconeogenesis
what is thought to be the main glucose sensor in beta cells?
glucokinase
i.e. hexokinase IV
explain the process by which insulin secretion from pancreatic beta cells is controlled
(when blood glucose is high)
increased blood glucose concentration
= increased glucose uptake into beta cells via GLUT2 channels
= increased conversion of glucose to G6P via glucokinase
= reduced ATP (and increased ADP)
= reduced activation of ATP-sensitive K+ channels so they remian closed
= intracellula K+ conc remains high
= increased activation of Ca2+ channels
= increased intracellular Ca2+ influx
= stimulates increased insulin secretion into the bloodstream
how is proinsulin converted into insulin?
proinsulin undergoes proteolytic cleavage into insulin
compare the structure of proinsulin and insulin
proinsulin = A chain + B chain + C-peptide
insulin = just A chain + B-chain (the C-=peptide is cleaved off)
a healthy person eats a Big Mac meal
what would you expect to happen to their C-peptide?
increases
a person with Type 1 diabetes mellitus eats a Big Mac meal
what do you expect their C-peptide to be?
should increase but stays LOW
what is the gastrointestinal ‘incretin’ effect?
when glucose is taken orally rather then intravenously
= in response to the nutrient ingestion, incretin is released
= stimulates insulin secretion even more
= higher plasma insulin levels are seen after an oral glucose load rather than an IV glucose load
what is GLP-1?
a gut hormone secreted in response to nutrients in the gut
= stimulates insulin, inhibits glucagon
what is the function of GLP-1?
1) stimulates insulin, suppresses glucagon
2) promotes satiety (‘fullness’)
from where is GLP-1 secreted?
mainly L cells
short half life due to DPP-4 enzyme
why is GLP-1 important?
used in the treatment of diabetes
= DPP-4 inhibitor will delay the degradation of GLP-1 so it remains within circulation longer to increase insulin secretion and keep glucagon secretion suppressed
what is first-phase insulin release?
the initial burst of insulin, which is released in the first 5–10 min after the β-cell is exposed to a rapid increase in glucose
how does the first-phase insulin release compare in a healthy person and one who has T2DM?
healthy = huge burst of insulin released in the first 10 mins following glucose increase
T2DM = the increase in insulin is not as larger or rapid
what does insulin bind to?
insulin receptor (extracellular domain)
what is the structure of the insulin receptor?
1) alpha subunit (extracellular)
2) beta subunit (through cell membrane + and intracellular)
what occurs once insulin binds to its receptor?
insulin binds to the extracellular alpha subunit of the insulin receptor
= binding causes a conformational shape change in the tyrosine kinase domains of the beta subunits
