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Flashcards in 5. Insulin Deck (52):
1

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

2

preproinsulin is synthesized (where )

RER

3

proinsulin is stored ( where )

stored is secretory granules

4

insulin and C peptide are increased in ( situations )

1. insulinoma
2. sulfonylurea

5

proinsulin structure

β chain - c peptide - α chain
β chain is linked with α chain wit S-S bonds

6

Insulinoma vs exogenous insulin

insulinoma ( or sulfonylurea):
increased C peptide and insulin exogenous insulin : not increased C- peptide

7

insulin is released from

pancreatic β cells

8

insulin receptor type

tyrosine kinase activity

9

insulin- steps of action ( generally)

binds to insulin receptor --> inducing glucose upatke ( carrier mediated transport ) into insulin depended tissue and gene transcription

10

anabolic effect of insulin

1. increased glucose transport in skeletal muscle and
adipose tissue
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

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effect of insulin kidneys

increased Na+ retention

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effect of insulin in K+

increased cellular uptake

13

effect of insulin in aminoacids

increased cellular upatake

14

glucose vs insulin ( placenta)

glucose cross placenta
INSULIN DOES NOT CROSSPLACENTA

15

Insulin - independed glucose transporters

Glut-1
Glut-2
Glut-3
Glut-5

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insulin - depended glucose transporters

Glut-4

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Glut-4 - area

1. adipose tissue
2. striated mucle ( --> exercise also increases them)

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Glut-4 expression can be increased by

exercise

19

Glut-1 area

1. RBCs
2. Brain
3. Cornea
4. Placenta

20

Glut -2 - special feature

bidirectional

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GLut - 2 - are

1. β islet cells
2. liver
3. kidney
4. small intestine

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Glut -3 - area

brain, placenta

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Glut -5 special feature

fructose

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Glut -5 area

spermatocytes
2. GI tract

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brain - " food"

brain utilizes glucose for metabolism normally and ketone bodies during starvation

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RBCs - " food"

utilize glucose

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RBCs utilize ..... why

glucose
they lack mitochondria for aerobic metabolism

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Brain - GLUT

1 and 3

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spermatocyte - glut

5

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cornea - Glut

1

31

placenta Glut

1+3

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Glut for fructose

5

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Glut - biderectional

2

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the major regulator of insulin release

glucose

35

Insulin release regulator s ( and how )

1. glucose ( increases
2. GH ( increases )
3. β2 agonists ( increase)
4. cortisol ( increase)
5. α2 agonists --> decrease
insulin release

36

GH insulin regulator (pathophysiology

GH cause insulin resistance ---> increases insulin release

37

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 .

38

insulin induce gene transcription - pathway

insulin --> receptro --> tyrosin phosphorylation --> RAS/MAP kinase pathway --> cell growth , DNA synthesis

39

Insulin induce glucose uptake

insulin ---> receptro --> phosphorylation --> phospoinositide - 3 kinase pathway --> glycogen, lipid , protein synthesis and vesicles that contain GLUT 4 in the membrane

40

cortisol - insulin regulation

causes insulin resistance --> increases insulin release

41

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

42

• 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)

43

• 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

44

• 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

45

• Other than glucose, which hormones/chemicals increase or decrease insulin production?

Growth hormone and β2-agonists increase insulin; somatostatin and α2-agonists decrease insulin

46

• 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)

47

• 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

48

• 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

49

• 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

50

• 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

51

• 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).

52

• In most tissues, insulin is required to move glucose into cells. Which tissues are exceptions and can take up glucose without insulin?

Brain, RBCs, Intestine, Cornea, Kidney, Liver (BRICK L) have insulin-independent glucose uptake