Regulation of Glucose Flashcards
What happens to glucose in the fed state and fasting state?
Fed state - excess glucose is stored as glycogen
Fasting state - mobilized
What is an important contributor of glucose in the fasting state?
Gluconeogenesis (liver)
What is insulin and where is it secreted?
Insulin is a peptide hormone secreted from the beta cells of the pancreas.
What triggers the release of insulin?
Secretion triggered by entry and metabolism of glucose into pancreatic beta cells.
Describe how glucose is released.
When concentration outside cell is higher than 5.5 mol
Entry via GLUT-2 and metabolism of glucose into beta cells (pancreas)
Subsequent increase in ADP/ATP
Tiggers calcium influx and activation of proteins involved in trafficking of sensory granules
Sensory granules release insulin
Describe the formation/previous forms of insulin.
Preproinsulin - how insulin starts out.
Preproinsulin changes to proinsulin and signal peptide (secretory signal is clipped off)
Cleavage of C peptide changes to C-peptide and insulin
What is important to note about C-peptide in the clinical setting?
C-peptide levels show you how much insulin a patient is producing
When insulin is injected, the C-peptide is removed
Therefore C-peptide levels are purely endogenous
What do the alpha cells of the pancreas produce?
Glucagon
What do the beta cells of the pancreas produce?
Insulin
What do the delta cells of the pancreas produce?
Somatostatin
What type of receptor is an insulin receptor?
Tyrosine kinase receptor - an enzyme that phosphorylates particular tyrosines found on its substrates (adds phosphate to tyrosine on proteins)
How are the effects of insulin mediated?
Through an intracellular signalling cascade that either changes phosphorylation status or alters transcription or alters transcription of several enzymes involved in fuel metabolism
Describe the general effects insulin has on the liver, muscle and fat cells.
Fat - lipogenesis
Muscle - glycogen synthesis (glycogenesis)
Liver - lipogenesis and glycogen synthesis (glycogenesis)
What stimulates/inhibits and potentiates insulin secretion from B cells?
Stimulates - glucose >5mmol/L, arginine, alanine, glycine
Inhibits - adrenaline, glucagon
Potentiated by hormones e.g. cholecystokinin and other gut hormones (incretins)
What is the incretin effect?
Delivery of oral glucose to the small intestine gives a higher insulin response than IV glucose
What are incretins?
Gut hormones that help control blood glucose levels
Some stimulate insulin release
Some alter nutrient absorbance rate from the gut
Some affect appetite
List examples of incretins.
Glucagon-like peptide 1 (GLP-1)
Gastric inhibitory peptide (GIP)
List the insulin effect on fuel metabolism.
- Promote glucose uptake by activating GLUT4 in muscle and adipose
- Promotes glycogen synthesis (liver, muscle) and lipogenesis (liver, adipose)
- Promote glucose utilization (glycolysis - breaks down glucose)
- Inhibits gluconeogenesis (liver) and glycogenolysis (liver and muscle) & lipolysis (adipose)
- Stimulates LPL activity to promote fatty acid reuptake by adipose. Inhibits hormone sensitive lipase (breaks down fats)
- Promotes amino acid uptake
What is the difference between GLUT 2 and GLUT 4
GLUT 4 - insulin sensitive (muscle and adipose)
GLUT 2 - glucose sensitive (liver)
What effects does insulin have on the liver?
Increase glycogen synthesis
Increase lipogenesis
Decrease gluconeogenesis
What effects does insulin have on the muscle?
Increase glucose uptake
Increase glycogen synthesis
What effect does insulin have on the adipose tissue?
Increase glucose uptake
Increase lipoprotein lipase
Increase TAG storage
Decrease lipolysis
What effect does insulin have on the pancreas?
Alpha cells - decrease glucagon synthesis
Describe the regulation of glycogen synthase in the fed state?
Activated by insulin
- Promotes dephosphorylation by activating phosphatase, PP1 that converts glycogen synthase enzyme to its dephosphorylated form
Activated by glucose, glucose-6-phosphate
