Insulin, Glucagon and Somatostatin Flashcards
What are the three cells found in the pancreas?
Alpha cells
Beta cells
Delta cells
What do alpha cells secrete?
Glucagon
What do beta cells secrete?
Insulin
What do delta cells secrete?
Somatostatin
What is insulin produced as?
Pre-proinsulin -> proinsulin -> Insulin + C-peptide
What mineral is required for insulin formation?
Zinc (Zn2+)
What two things are released with insulin?
Zinc
C-peptide
What is C-peptide?
It is the part of the prohormones of insulin that is cleaved and secreted also
What is C-peptide used for?
A marker to help determine how much insulin a diabetic’s pancreas is producing
What two things can C-peptide levels help with?
Newly diagnosed type I diabetic
Type II diabetic whose insulin production is being boosted by drugs
Half-life of C-peptide compared to insulin?
Much longer
What glucose transporter is most abundant in beta cells?
GLUT-2
Where is GLUT-1 found?
On all cells
What is the importance of GLUT-1?
Fastest transporter/works at lowest concentration of glucose and is important at fasting blood glucose levels
Where is GLUT-2 found?
Liver
Pancreas
Intestines
What is the importance of GLUT-2?
Immediately after a meal when glucose is increased and during gluconeogenesis when intrahepatic glucose is increased
Where is GLUT-4 found?
Muscle
Fat
Heart
What is the importance of GLUT-4?
After a meal when insulin is released
What two enzymes phosphorylate glucose and where are they found?
Hexokinase: extrahepatic cells
Glucokinase: liver only
Glucokinase has a higher Km, what does this mean?
It needs more glucose levels in order to work
Glucokinase higher Km importance?
It can only sequester glucose in the liver for glyconeogenesis when glucose is higher in concentration so when it is in low concentration the hexokinase in extrahepatic cells can still take in the glucose without the liver stealing it all
What controls the secretion of insulin?
The amount of glucose coming in and being converted to ATP
What is the mechanism for insulin release?
Glucose enters via GLUT-2 in beta cells-> glucose converted to ATP-> increased ATP/ADP-> ATP sensitize K channel closes-> cell depolarized-> depolarization of cell causes voltage Ca channel opening-> Ca enters the cell-> Ca triggers vesicular release of insulin
Where are sulfonylurea receptors found?
Surrounding the ATP sensitive K channel on beta cells
What does sulfonylurea receptor stimulate?
Secretion of insulin by closing the ATP sensitive K channel
What do you use sulfonylurea drugs for?
Type II diabetes only
What are two sulfonylureas?
Glyburide (drug of choice)
Tolbutamide
Two SUR receptors and where they’re found:
SUR1: Beta cells
SUR2: all type of muscle cells
What drug inhibits secretion of insulin in cases of hypoglycemia?
Diazoxide
What causes a larger secretion of insulin oral or IV glucose?
Oral glucose
Why does oral glucose cause a larger increase in insulin?
GI hormone release GLP-1 and GIP
What are incretins?
GLP-1
GIP
What secretes GLP-1?
L cells in small intestine
What does GLP-1 cause?
An increase in insulin secretion
What is the primary stimulus for GLP-1 release?
Free fatty acids and glucose
What can GLP-1 be used to treat?
Diabetes Type II
What is the primary stimulus for GIP release?
Free fatty acids
TAGs
Glucose
AA
What cells release GIP?
K cells in the small intestine
What does GIP cause?
Insulin secretion
What receptor do GIP and GLP-1 work on?
GPCR-> adenylate cyclase pathway
What two receptors from SNS have an affect on insulin release and what are the effects?
Beta-2: augments
Alpha-2: inhibits
What do free fatty acids in the blood cause?
Stimulate insulin release
What receptor do FFA bind to in beta cells?
GRPAD/FFA1/GPR40
all three the same
What does GRPAD being bound cause intracellularly?
Gq receptor so PLC-> IP3-> Calcium intracellularly
What do the alpha and beta subunits of insulin have?
Disulfide bonds
What type of receptor are the IRS (insulin receptors)?
Tyrosine kinase receptors
What three things can the IRS tyrosine kinase receptors phosphorylate?
SHC
SH2
The SH2 domain on what two molecules gets phosphorylated?
GRB2
PI3K
What is the sequence of events once GRB2 is phosphorylated?
GRB2 -> SOS-> Ras-> Raf-1 (kinase)-> phosphorylates MEK (kinase)-> MAPK-> nucleus for transcription
What occurs when SHC is phosphorylated?
It activates SOS
What occurs when PI3K is phosphorylated?
Activates PDK-> phosphorylates PKB-> recruits GLUT-4 to the cell membrane
What are the overall affects of GRB2 and PI3K?
GRB2: transcription of genes
PI3K: activity of enzymes
What does PDK also activate?
mTOR
What does mTOR do?
Increases protein synthesis and decreases proteolysis (insulin as a growth factor)
What does PKB do?
Recruits GLUT-4
Activates glycogen synthase kinase
What is a peptide released with insulin?
Amylin
What does amylin do?
Reduces the secretion from all three pancreatic cell types acting as a safety mechanism
What affect does amylin have on the stomach?
It slows gastric emptying and promotes satiety
What is the overall affect of amylin?
Slow the appearance of glucose in the blood after eating and therefore reduces food intake
What can occur with proamylin?
It is concentrated in vesicles so it can lead to apoptosis leading to Type II diabetes
What would proamylin become too concentrated in vesicles?
In times of high demands
What GLUT is on alpha cells?
GLUT-1 not GLUT-2
What is the importance of GLUT-1 on alpha cells and not GLUT-2?
It transports glucose when it is at all concentrations
What is the mechanism of glucagon release from alpha cells?
Glucose is coming in at all levels-> low amounts of ATP-> slight closing of the ATP sensitive K channel-> slight depolarization-> unique T-type Ca channel open to depolarize membrane just a little-> Na channels respond and depolarize membrane enough to open L/N- Ca channels-> glucagon released
What are special channels only found in alpha cells needed from glucagon release?
T-type Ca channels
L and N-type Ca channels
Na channels
Why don’t alpha cells release glucagon all the time if glucose is always present?
Because once beta cells do get stimulated they secrete insulin which inhibits secretion from alpha cells
What are three things that inhibit glucagon secretion?
Insulin
Zinc 2+
Somatostatin
What type of receptor does glucagon bind to?
GPCR-> AC-> cAMP
What are the two active forms of somatostatin (SS)?
SS-14
SS-28
What SS does the stomach and intestinal tract secrete?
SS-28
What SS does the nervous system secrete?
SS-14
Sole form of SS secreted from pancreas?
SS-14
Which SS inhibits growth hormone?
SS-28
Which SS inhibits glucagon release?
SS-14
What cells in the stomach release SS?
D cells
What cells in the pancreas release SS?
Delta cells
Where are each of the 5 SS receptors (SSTR) located?
SSTR1: stomach and jejunum SSTR2: cerebrum and kidney SSTR3: brain and pancreatic islet SSTR4: fetal and adult brain and lung SSTR5: pancreatic islets
Actions of SS on the anterior pituitary?
Inhibit release of:
GH
TSH
PRL
Action of SS on pancreas?
Inhibits release of:
Insulin and glucagon
CCK release
Secretin and HCO3
Affect of SS on the stomach?
Decrease rate of gastric emptying, motility, blood flow
What is a somatostatinoma?
Tumor that produces somatostatin
What would a somatostatinoma cause from affects on pancreas and GI tract respectively?
Pancreas: decreased insulin so diabetes
GI tract: CCK suppression and decreased GB contraction so gallstones
What would a SS deficiency cause?
Excess GH secretion
