Endocrine Pancreas Flashcards
What are the endocrine cells in the pancreas and what do they secrete?
alpha = glucagon
beta = insulin, C peptide
delta = somatostatin
How are the endocrine cells arranged in islets?
betas in the center
alpha and delta in the periphery
(alpha and delta get bathed in insulin)
What does sympathetic stimulation do to the pancreas?
Parasympathetic?
alpha adrenergic signal –> decreased insulin
ACh –> increased insulin
How do cells of pancreatic islets communicate with each other?
gap jxns = rapid cell-to-cell communication btw a-a, a-b, b-b
blood flows into center of islets first –> goes out = all cells get bathed in insulin
How do delta cells affect beta and alpha cells?
somatostatin inhibits insulin and glucacon secretion
How do beta cells affect alpha and delta cells?
beta cells inhibit alpha cells
alpha cells promote insulin
delta cells inhibit beta cells
How are the alpha and beta strands of insulin held together?
by 2 disulfide bridges
C peptide initially holds them together but is then cleaved to form the active hormone
What is the main stimulus for insulin?
carbohydrate or protein-containing meal –> high glucose levels
What is the difference between preproinsulin, proinsulin, and insulin?
preproinsulin = signal peptide, A and B chains, and connecting peptide
proinsulin = no signal peptide; C peptide, disulfide bridges form in ER –> packaged in vesicles in golgi
during packaging, proteases cleave proinsulin
What is the importance of C peptide?
insulin and C peptide are packed together in secretory vesicles –> secreted in 1:1 ration
C peptide can be used as long-term marker of Beta cell function and insulin secretion
How does glucose signal insulin release?
glucose binds glut2 – glucokinase –> G-6-P –> makes ATP –> closes K+ channels –> cell depolarizes –> voltage-gated Ca channels open –> exocytosis of insulin and C peptide
What do sulfonurea drugs do?
promote the closing of ATP-dependent K+ channels (glucose signals this) –> so that more insulin will be secreted
used to treat T2DM
How is insulin secreated in response to glucose?
biphasic manner
phase 1 = preformed vesicles released
phase 2 = preformed and newly synthesized insulin released
In diabetic ppl, what is the first thing to disappear?
the first phase/ acute insulin response
How do CCK and ACh contribute to insulin release?
both bind Gq receptor –> PLC –> IP3 and DAG –> both calcium and PkC signal insulin release
How does somatostatin contribute to insulin release?
binds Gi –> inhibits cAMP and PkA –> inhibits insulin release
How do glucagon and GLP-1 contribute to insulin release?
Binds Gs receptor –> cAMP –> PkA –> insulin release triggered
What happens (in general) when insulin binds its receptor?
receptor phosphorylates itself and other proteins –> insulin-receptor complex is internalized by target cell –> glucose transport, protein, fat, and glycogen synthesis; growth and gene expression
How does insulin affect its own receptor?
down regulates its own receptor
What is the relationship btw insulin and the liver?
insulin released from pancreas –> to liver, can take up insulin and receptor and cleave –> actual levels in systemic circulation are a lot less than what is initially released from the pancreas