Flashcards in 5. Insulin Deck (52)
Insulin structure pathway
preproinsulin ( synth in RER) --> cleavage or signal --> proinsulin ( stored in secretory granules ) ---> clevage of proinsulin ---> exocytosis of insulin and C-peptide equally
preproinsulin is synthesized (where )
proinsulin is stored ( where )
stored is secretory granules
insulin and C peptide are increased in ( situations )
β chain - c peptide - α chain
β chain is linked with α chain wit S-S bonds
Insulinoma vs exogenous insulin
insulinoma ( or sulfonylurea):
increased C peptide and insulin exogenous insulin : not increased C- peptide
insulin is released from
pancreatic β cells
insulin receptor type
tyrosine kinase activity
insulin- steps of action ( generally)
binds to insulin receptor --> inducing glucose upatke ( carrier mediated transport ) into insulin depended tissue and gene transcription
anabolic effect of insulin
1. increased glucose transport in skeletal muscle and
2. increased glycogen synthesis and storage
3. increased triglyceride synthesis
4. increased Na+ retention (kidneys)
5. increased protein synthesis (muscles)
6. increased cellular uptake of K+ and amino acids
7. decreased glucagon release
8. decreased lipolysis in adipose tissue
effect of insulin kidneys
increased Na+ retention
effect of insulin in K+
increased cellular uptake
effect of insulin in aminoacids
increased cellular upatake
glucose vs insulin ( placenta)
glucose cross placenta
INSULIN DOES NOT CROSSPLACENTA
Insulin - independed glucose transporters
insulin - depended glucose transporters
Glut-4 - area
1. adipose tissue
2. striated mucle ( --> exercise also increases them)
Glut-4 expression can be increased by
Glut -2 - special feature
GLut - 2 - are
1. β islet cells
4. small intestine
Glut -3 - area
Glut -5 special feature
Glut -5 area
2. GI tract
brain - " food"
brain utilizes glucose for metabolism normally and ketone bodies during starvation
RBCs - " food"
RBCs utilize ..... why
they lack mitochondria for aerobic metabolism
Brain - GLUT
1 and 3
spermatocyte - glut
cornea - Glut
Glut for fructose
Glut - biderectional
the major regulator of insulin release
Insulin release regulator s ( and how )
1. glucose ( increases
2. GH ( increases )
3. β2 agonists ( increase)
4. cortisol ( increase)
5. α2 agonists --> decrease
GH insulin regulator (pathophysiology
GH cause insulin resistance ---> increases insulin release
insulin secretion by pancreatic β- cells - mechanisms
1. Glucose enters β cells (via Glut2) ---> 2) ATP generated from glucose metabolism 3. closes K+ channels (target of sulfonylureas) and 4. depolarizes β cell membrane .5. Voltage-gated Ca2+ channels open
--> Ca2+ influx and 6. stimulation of insulin exocytosis .
insulin induce gene transcription - pathway
insulin --> receptro --> tyrosin phosphorylation --> RAS/MAP kinase pathway --> cell growth , DNA synthesis
Insulin induce glucose uptake
insulin ---> receptro --> phosphorylation --> phospoinositide - 3 kinase pathway --> glycogen, lipid , protein synthesis and vesicles that contain GLUT 4 in the membrane
cortisol - insulin regulation
causes insulin resistance --> increases insulin release
insulin release in oral vs IV glucose
greater in oral because of icretins such GLP -1 which are released after meals and increase β cell sensitivity to glucose
• What type of GLUT is used by β islet cells, the liver, kidney, and small intestine? What other tissues use glucose transporters?
GLUT-2 (bidirectional) = RBCs/brain; GLUT-1 (no insulin) = adipose/skeletal muscle; GLUT-4 (needs insulin); GLUT-5 (fructose, no insulin)
• What is the effect of insulin on electrolyte (Na+, K+) and amino acid handling?
Increases Na+ retention by the kidneys and shifts both K+ and amino acids into cells
• What effects does insulin have on glucose, glycogen, protein, and lipid production and storage?
Increased muscle and adipose glucose transport; increased glycogen/triglyceride synthesis and storage; increased muscle protein synthesis
• Other than glucose, which hormones/chemicals increase or decrease insulin production?
Growth hormone and β2-agonists increase insulin; somatostatin and α2-agonists decrease insulin
• A pregnant woman with type 1 diabetes mellitus injects insulin before a meal. How does this insulin affect her fetus?
Does not directly affect the fetus, because insulin doesn't cross the placenta; glucose level does affect the fetus, however (indirectly)
• What effect would a drug that keeps K+ channels open have on insulin release?
It would decrease it; K+ channel closure ultimately stimulates insulin exocytosis from pancreatic β cells
• A student studies 24 consecutive hours without eating. What fuel does his brain use during starvation? Why can't RBCs do the same?
The brain uses ketone bodies during starvation; RBCs cannot do this, because they lack mitochondria for aerobic metabolism
• A friend tells you to add dextrose to your post-workout shake. He says muscles take up energy well at this time. Via what mechanism?
GLUT-4 receptor expression on striated muscle and adipose tissue increases after exercise, so glucose is taken into cells most efficientlυ
• A newborn has a congenital dysfunction of her GLUT-3 transporters. What tissue type will be most affected by this?
Brain; GLUT-3 is an insulin-independent transporter of glucose in the brain
• The cornea has a insulin-independent transporter known as ____; spermatocytes use the insulin-____ (independent/dependent) GLUT-5 transport.
The cornea has a insulin-independent transporter known as GLUT-1; spermatocytes use the insulin-independent GLUT-5 transport (for fructose).