Glucose homeostasis Flashcards
why is glucose importabt and what happens in levels fall
important energy substrate
especially for Cns
If falls below norm (4-5 mmol/L ) - hypoglycaemia then cerebral function impaired
<2 mmol/L - unconsciousness, coma and death
what increases blood gluc
glucagon
cortisol
GH
catecholamines
What decreases blood gluc
insulin
persistant hyperglycaemia =
diabetes mellitus
What is mody
Maturity-onset diabetes of the young
caused by mutation in single gene
T2DM>T1DM>MODY
pancreas gland is a ….. structure
+ diagram
retriperitoneal
what is pancreas made up of
most (98%) generates exocrine secretions via duct to small intestine: exocrne acinar cells
2% are islets of Langerhands
These cells secrete and inc/ dec gluc
alpha cells -
beta cells -
delta cells -
a - glucagon - inc
b - insulin - dec
d- somatostatin - inhibits insulin and glucagon via paracine action
paracrine communication
Gap junctions : allow small molecules to pass directly between cells
Tight junctions : create small intercellular spaces
Communication occurs across gap junctions and tight junctions
tells cells how much hormone they need to be producing
what are pp cells
pancreatic polypeptide cells
inhbit pancreatic secretion
secrete somatostatin
why is insulin important
Why is somatostatin important
stimulates growth and development (important for fetal growth and development)
Somato- keeps both ins and glucagon in balance ; -ve feedback hormone
What does and what doesn’t increase activity of beta cells and therefore production of insulin
Increases:
- some aa
- some GI hormones
- alpha cells and glucagon
- SNS activity via beta cells
- PNs activity
Decreases :
- Somatostatin
- SNS activity via alpha cells
What does insulin do
increased aa transport and protein synthesis
Decreased lipolysis and increased lipogenesis
Increased glycogenesis so
Increased glycolysis
so Increased gluc transport into cells via GLUT-4
What does or doesn’t increase activity of alpha cells and therefore production of glucagon
Increases
- some aa
- some GI hormones
- blood glucose
- SNS activity via alpha cells
- PNS activity
Decreases :
- beta cells and insulin
- Somatostatin
What does glucagon do
- Increased aa transport into liver +
- Increased lipolysis
- so Increased glucongeogenesis
- Increased hepatic glycogenesis
What is main glucose sensor on beta cell
Glucokinase (hexokinase IV) - only hexokinase not subject to -ve feedback - so gluc 6 phosphate does not inhibit this
glucokinase converts gluc to G6P - allows the cell to ‘see’ the gluc conc so a rise in G6P causes insulin synthesis and release - why we say this hormone is the glucose sensor.
GLUT-2 is not insulin sensitive
How does beta cells know it needs to increase insulin production to maintain blood gluc
- GLUT2 - high affinity for gluc
- Gluc in blood is reflected in intracellular conc of beta cells
- Gluc Converted to glucose 6 phosphate - First stage of glycolysis
- mediated by glucose kinase
- Converted to ATP (xtracellular gluc = intracellular gluc = intracellular ATP)
- ATP-Sensitive K+ Channel is blocked by the ATP. Closes potassium gated channels
- K remains intracellular , prevents extracellular flux of K, Increase in K
- Memb depolarisation
- Opens calcium voltage gated channels, Influx of CA
- Ca2+ causes the vesicles containing insulin to migrate to the cell membrane and fuse with it, releasing pre-formed insulin. Promotes insulin secretion.
- Not all or nothing process - graded response
- More gluc = more insulin
- Gluc varies constantly so amount of insulin made depends on conc of gluc
What is c peptide
pro insulin is cleaved to form insulin and c peptide
There is 1:1 ratio of these two
insulin difficult to measure in blood so c peptide is measured using blood tests
in someone with diabetes c peptide is
low
insulin is also low
what is GLP-1
- glucagon like peptide -1
- Gut hormone
- Secreted in response to nutrients in gut
- Transcription product of pro-glucagon gene, mostly from L-cell
- Stimulates insulin, suppresses glucagon
- ↑ satiety (feeling of ‘fullness’)
- Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor)
- Used in treatment of diabetes mellitus
does oral gluc lead to higher increase in insulin as opposed to IV gluc ?
yes
because GLP-1 in gut
stimulates insulin
IV glucose bypasses that
so less insulin secretion
first phase insulin release
FPIR
when insulin stored in pancreas is released immediately after a meal
Effects lasts for 10-15 mins
T2D - don’t have this
Insulin receptor
- Insulin binds to extracellular domain for insulin receptor (alpha subunit)
- there is conformational change in the tyrosine kinase linked domains of the beta subunits (via auto and crossphosphorylation)
- 2 alpha, and 2 beta subunits. This receptor is Tyrosine-kinase linked.
