Insulin, glucagon, GLP1, CRH Flashcards
Cell types of the pancreas: B cells secrete? a cells secrete? delta? PP?
B: insulin
- arranged around central core
a-cells: secrete glucagon
Delta: somatostatin
PP:
pancreatic polypeptide
What is exposed to higher levels of insulin and glucagon?
Liver, muscle, or adipose?
Liver
- secretion products of the pancreatic cells goes into the portal vein and into the liver first
Where are C peptides cleaved when insulin is being synthesized/processed? Why is this significant?
C-pep is cleaved in the secretory vesicles after it leaves the golgi
It is secreted into the blood stream along with insulin
Biphasic response of insulin secretion
first phase:
secretion of vesicles of insulin already docked at pm
second phase:
recruitment of cytoplasmic vesicles to the docked position
- will surge if islet cells are responding to high glucose [ ] for 20 min or longer
Initiators of insulin release
deez guys stim insulin release on their own!
glucose
aa
drugs - sulfonylureas
Potentiators
stim insulin secretion only in presence of glucose
(potentiate glucose effect on insulin)
glucagon
incretin (GLP-1)
acetylcholine
Inhibitors of insulin secretion
diazoxide
somatostatin
alpha adrenergic agents
- Long term FA exposure
- Long term hyperglycemia
(glucose toxicity)
How does glucose lead to insulin release?
- Glucose enters beta cell
- Glucose is metabolized by glucokinase to G6P
- ATP is eventually made (phosphoglycerate and pyruvate)
- Closing of ATP regulated potassium channels
- depolarization –> VGCC activation + exocytosis of insulin
Somatostatin effect on insulin release
somatostatin is made by delta cells, and decreases insulin release
(just like catecholamines and splanchnic n does)
Stimulation of the splanchnic nerves does what to insulin secretion?
Inhibits insulin secretion
just like catecholamines and somatostatin does
Stimulation of the vagal n with release of ACh has what effect on insulin?
Increase insulin secretion
- This increases insulin with the sight or first taste of food “cephalic phase” of insulin release
Which type of diabetes has both insulin resistance and insulin deficiency?
T2D
- early in the course, insulin deficiency is ‘relative’
- insulin lvls are high but not high enough to lower blood glucose levels
- later in the course, insulin lvls are lower than normal
Glucose uptake into cells are stimulated by insulin in all but where?
Skeletal m, adipose
not in liver, or brain
How does insulin signaling occur ? What effect does it have on the insulin receptor?
The insulin receptor = EGF family, heterotetramer
- signaling occurs with autophosphorylation of the receptor and other substrates (aa, tyr residues).
- The P of insulin receptor substrates (IRS) forms the main links for signal transduction btwn rcptr and downstream effector pathways
- IRS = dockin site for SH2 domain proteins
- Results in metabolic or mitogenic effects
Example of Metabolic pathway activation of insulin release
after auto P and P/activation of IRS –>
stimulates PI3K –>
rapid translocation of GLUT4 into insulin sensitive PM (skeletal/adipose) –>
stim glucose uptake
Mitogenic pathway key intermediate
Insulin Receptor Substrates (IRS) –> Map KINASE
not PI3K like in metabolic
How can glucagon secretion be inappropriately high in T1D and T2D?
T1D - insulin is low
T2D - insulin resistance
GLP-1 analogues help control hyperglycemia how?
reduce glucagon levels
it imitates GLP-1 which it ups insulin response by 50-70% + release
Incretin is responsible for how much of the insulin response to oral glucose ingestion
50-70%
GLP1 actions
- Increase insulin secretion when glucose is high only
- inhibits glucagon secretion
- inhibits GI secretion and motility
- inhibits appetite and food intake
Will GLP-1 result in weight gain or loss?
Loss - it reduces appetite and does not cause hypoglycemia
How are catecholamines different from glucagon in increasing blood glucose?
They affect similar cAMP pathways, but also:
- inhibit insulin secretion
- produce insulin resistance in skeletal m by stim glycogenolysis
- super helpful with hypoglycemia
Catecholamines are elevated during?
DKA
stress
surgical stress
trauma
Is cortisol response fast or slow?
slow - MOA requires protein synthesis
It is secreted in response to virtually all stressful stimuli
Actions of cortisol (3)
- increase supply of aa available as subtrates but promoting breakdown in m
- inhibits insulin action
- potentiates actions of glucagon and catecholamines
Chronic use of which can lead to diabetes?
Glucagon,
Catecholamines,
Cortisol
Cortisol/corticosteroids -
its anti insulin effects
How does GH (one of the 4 CRH) reduce hypoglycemia?
promotes lipolysis and stim of protein synth
- promote utiliz of proteins
antiinsulin effect
- insulin R can be seen in adolescents with growth spurt or GH tumors
