Week 4- Glucose Homeostasis Flashcards
What blood glucose level causes cerebral function to be impaired?
Below 4-5 mmol/L
What blood glucose level causes coma?
< 2 mmol/L
What is the most prevalent type of diabetes mellitus?
Type 2
What type of structure is the pancreas gland?
Retroperitoneal
What are the 3 types of cells found in islets of Langerhans? What hormone do each of these cells produce?
Alpha-glucagon
Beta-insulin
Delta-somatostatin
What are the actions of insulin?
Reduces blood glucose, encourages growth and development
What is special about GLUT 2?
It is not insulin sensitive
How is insulin secreted from beta cells?
Glucose enters beta cell via GLUT 2
Glucose 6 phosphate generated from glucose via glucokinase enzyme (rate limiting step)
ATP generated
ATP inhibits potassium channel
Potassium level in cell rises
Intracellular potassium opens calcium ion channel
Influx of calcium causes stored insulin release and synthesis of more insulin
How is insulin synthesised?
The precursor proinsulin undergoes proteolytic cleavage to form C peptide and insulin
What is C peptide a marker of?
Endogenous insulin
What hormone is involved in the incretin effect?
Glucagon like peptide-1 (GLP 1)
What happens to levels of GLP-1 in type 2 diabetics?
Levels are lower
What does the insulin receptor compose of?
An alpha subunit (extracellular domain that insulin binds to) and a beta subunit
What do most cells of the pancreas do?
Generate exocrine secretions to the small intestine
What is insulin inhibited by?
Somatostatin
What is glucagon inhibited by?
Somatostatin
What does glucagon do?
Increases blood glucose
What stimulates beta cells to produce insulin?
Increased blood glucose
Some amino acids from food that has been eaten
Some GI hormones
PNS activity
What inhibits beta cells from producing insulin?
SNS activity (although minor stimulation still occurs) Delta cell production of somatostatin
How does insulin effect blood glucose?
It increases glycogenesis, glycolysis and glucose transport into cells via GLUT4
Overall this reduces blood glucose
How does insulin effect lipid levels?
It decreases lipolysis
It increases lipogensis
How does insulin effect protein levels?
It increases amino acid transport
It increases protein synthesis
What stimulates alpha cells to produce glucagon?
Reduction in blood glucose Some amino acids via diet Some GI hormones SNS activity PNS activity
What inhibits alpha cell production of glucagon?
Beta cell secretion of insulin
What physiological changes does glucagon cause?
Mainly increase in hepatic glycogenolysis
Increase in amino acid transport to the liver and lipolysis both of which increase gluconeogenesis
What is the rate limiting step in beta cells during insulin secretion? What is the name of the enzyme involved?
Conversion of glucose to glucose 6 phosphate
Enzyme involved is gluokinase
What is the incretin effect?
The phenomenon wherein plasma insulin levels increase much more significantly when glucose is given orally compared to intravenously due to the effects of GI hormones (mainly GLP-1)
What is GLP 1 and what are its effects?
Its a gut hormone secreted in response to certain gut nutrients, it stimulates insulin and surpresses glucagon, increases satiety (feeling of fullness)
What is a special property of GLP-1?
It has a short half life due to rapid degeneration from enzyme dipeptidyl peptidase 4
Why may GLP-1 be used in the treatment of diabetes and which type?
T2DM, it helps promote satiety which can help with weight loss commonly associated with T2DM and usually type 2s have lower GLP-1 anyways
How is first phase insulin release different in those with T2DM compared to normal people and why?
There is no spike in insulin levels after first phase glucose release in T2DM as they dont have as much stored insulin. They therefore have to synthesise new insulin which results in slower restoration of blood glucose that is also incomplete
What happens to the insulin receptor when insulin binds to it?
There is a conformational change in the tyrosine kinase domains of the beta subunits
