Control of blood glucose & endocrine pancreas Flashcards
How does glucose get into cells?
→ Secondary active transport
→ SGLT 1
→ Sodium transports glucose into the cell
How does glucose get reabsorbed in the kidney?
→ SGLT 1 and SGLT2
Where is GLUT 1 found and in what ranges does it work?
→ In the brain + erythrocytes
→ High affinity for glucose
→ Constant uptake at 2-6mM
Where is GLUT 2 found and what is the affinity like?
→ liver,kidney,pancreas,gut
→ Low affinity
→ Transport rate increases with glucose concentration
Where is GLUT 3 found and what is its affinity?
→Brain
→ High affinity
Where is GLUT 4 found and what is its affinity?
→ muscle and adipose tissue
→ Medium affinity
→ Insulin recruits transporters
What does high affinity mean?
→ rate of transport does not depend on the concentration
What are the islets of Langerhans?
→ Clusters of endocrine cells surrounded by an exocrine pancreas
what do alpha cells in the pancreas produce?
→ Glucagon
What do beta cells in the pancreas produce?
→ Insulin
What do the delta cells in the pancreas produce?
→ Somatostatin
What are the steps for insulin production?
1) original transcript is pre-pro insulin
2) Signal sequence is removed ( in RER)
3) Transferred to Golgi apparatus
4) Peptidases break off the C peptide leaving an A and B chain linked by disulfide bonds
For every mole that is secreted of insulin how many C peptides do you get?
one
What is the clinical significance of C peptide
→ It is inert
→ good index of insulin circulation
What is the blood supply of the pancreas?
→ Branches of celiac, superior mesenteric and splenic arteries
What is the venous drainage of the pancreas?
→ Into the portal system
Describe the path insulin takes
→ Insulin is secreted in circulation
→ drained into portal vein
→ Metabolized by the liver
→ remainder is diluted in circulation
Where is the insulin most concentrated?
→ in the portal vein
Why is C peptide a more accurate index of insulin secretion?
→ It is not metabolized by the liver
What stimulates the secretion of insulin from Beta cells ?
→ rise in plasma glucose → amino acids - arginine → Glucagon → Parasympathetic effects → Incretin hormones
What inhibits insulin?
→ Alpha adrenergic receptors
→ somatostatin
What stimulates glucagon secretion from alpha cells?
→ Amino acids
→ beta adrenergic
→ parasympathetic
What inhibits glucagon secretion?
→ Plasma glucose
→ Somatostatin
→ Insulin
How do beta cells sense a rise in glucose?
→ Increase in glucose through the GLUT 2
→ glucose is metabolized into ATP
→ ATP closes a K+/ATP channel
→ Depolarized the cell
→ Activates VG calcium channels
→ rise in iCa stimulates vesicular release of insulin
What family is the insulin receptor a part of?
→ Tyrosine Kinase
How does the insulin receptor work?
→ Insulin binds
→ Starts many protein activation cascades
What are the protein cascades activated by the insulin receptor?
→ Translocation of the GLUT 4 transporter to plasma membrane and influx of glucose
→ Glycogen synthesis
→ Glyolysis
→ Fatty acid synthesis
What enzyme starts lipogenesis and how?
→ACC starts lipogenesis
→ Insulin reduces PKA which inhibits ACC
Why is insulin resistance not down to one reason?
→ could be something highly selective
→ because there are many intracellular pathways
How does the glucagon receptor work?
→ Glucagon binds to its receptor
→ Adenylate cyclase converts ATP to cAMP
→ PKA is activated
How do insulin counter regulatory hormones work?
→ phosphorylation of enzymes
