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(1-5) Translational Medical Science > Trigger 1: Insulin secretion > Flashcards

Trigger 1: Insulin secretion Flashcards

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1
Q

Normal blood glucose

A

4-7mmol/l

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2
Q

When is blood glucose highest

A

after food

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3
Q

factors that affect BG

A

-exercise -food -illness -stress

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4
Q

Insulin

A
  • released from the B-cells in the islets of langerhans - increases uptake of glucose lowering blood sugar - stimulate glycogensis - inhibits glycolysis (Glycogen synthesis in skeletal muscle and liver and Increased lipogenesis and inhibition of gluconeogenesis in liver)
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5
Q

Glucagon

A

-released from alpha cells - increases blood glucose - inhibition of glycolysis and glycogenesis (i.e. decreases glycogen production) -stimulates glucoseneogenesis and glycogenolysis

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6
Q

receptor for glucagon is a

A

GPCR found on liver, increases cAMP and PKA

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7
Q

Beta cells

A

Insulin- decrease BG

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8
Q

Alpha cells

A

Glucagon- increase BG

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9
Q

When BG is high

A

1) beta cells stimulated to release insulin into blood 2) body cells and liver take up more glucose- stored as glycogen in liver 3) BG declines to a set point. Stimulus for insulin release diminished

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10
Q

When BG is low

A

1) Alpha cells stimulated to release glucagon 2) glucagon causes liver to break glycogen down and releases glucose into the blood 3) glucose level rises

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11
Q

How many GLUT transporters

A

14 main

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12
Q

GLUT 1

A

o Found in most cells. o Does not require insulin stimulation. o Facilitated diffusion of glucose o Works with GLUT3 to allow glucose across BBB

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13
Q

GLUT 2

A

o Transports glucose when BGL is high o Metabolic trigger to coordinate insulin secretion o LIVER and B cells

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14
Q

GLUT 3

A

o Brain o Higher affinity for glucose than other GLUTs

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15
Q

GLUT 4

A

o Liver, muscle and adipose tissues o Activated by Insulin signalling pathway o GLUT4 vesicles fuse with the plasma membrane and allows glucose to enter the cell

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16
Q

GLUT 5

A

o Intestinal tissue, kidney and spermatozoa o Fructose transporter

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17
Q

Which GLUT is activated during the insulin signalling pathway

A

GLUT 4

18
Q

which GLUT signals for B cells to release insulin

A

GLUT2

19
Q

action of glucagon

A

Increase BG - causes glycogen to break down in liver via glucagon receptors to increase cAMP and PKA - inhibits glycolyis and glycogenesis -stimulates glucoseneogenesis - prevent glycolysis

20
Q

insulin acts on

A

muscle, adipose and liver

21
Q

response to insulin has how many phases

A

2

22
Q

phase 1 of insulin release

A

initially rapid but transient bursts of insulin secretion. Probably due to the release of insulin from granules that directly adjacent to CM

23
Q

phase 2 of insulin release

A

If BGL remains high, then rise in insulin secretion is sustained due to the release of both stored and newly synthesises insulin

24
Q

Outline the molecular signalling cascade by which insulin promotes glucose uptake in adipose tissue

A

1) Insulin binds to receptor and causes dimerization and auto phosphorylation of tyrosine residues 2) Binding and phosphorylation of adaptor protein e.g. IRS 3) Activation of P13K, which phosphorylates PIP2 to PIPs 4) Phosphorylation of AKt 5) Causes GLUT4 vesicle to translocate to the cell membrane 6) Allows uptake of glucose from the blood stream by facilitated diffusion

25
Q

Activates PKb/AKT (insulin signalling pathway) causes

A

• GLUT4 translocation to the plasma membrane/glucose uptake in adipocytes and skeletal muscle • Glycogen synthesis in skeletal muscle and liver • Increased lipogenesis and inhibition of gluconeogenesis in liver

26
Q

2 types of stimulated insulin release

A

(1) Nutrient stimulated release (e.g. amino acids and fatty acids) (2) Neuronal stimulation of insulin secretion

27
Q

Nutrient stimulated release (e.g. amino acids and fatty acids)

A

• GLUT2 has a lower affinity for glucose than GLUT4

  1. ATP ( produced due to detection of insulin/ amino acids) causes B cell K+ channels to close
  2. Leading to membrane depolarisation (becomes more negative)
  3. Causing Ca2+ gates to open
  4. Ca2+ influx
  5. Release of insulin granules
28
Q

(2) Neuronal stimulation of insulin secretion

A

• Sympathetic- Prevents insulin secretion: o Inhibits cAMP, so PKA not activated • Parasympathetic- stimulates insulin secretion by stimulating Ach

29
Q

Sympathetic

A

Prevents insulin secretion: o Inhibits cAMP, so PKA not activated

30
Q

Parasympathetic

A

stimulates insulin secretion by stimulating Ach

31
Q

How are B cell specialised for insulin secretion? (5)

A

1) GLUCOKINASE
2) GLUT2 has a low affinity for glucose
3) Islets are highly vascularised to release insulin into the bloodstream
4) Number of B cells are tightly regulated
6) Highly differentiated- many unique TFs

32
Q

Glucokinase

A

is also known as hexokinase IV and catalyses the conversion of glucose to glucose 6 phosphate

33
Q

glucokinase is a key componenet of

A

glucose sensing machinery- - Sets the threshold for glucose stimulated insulin secretion

34
Q

characteristics of glucokinase

A

(1) Low affinity for glucose (S0.5 8-10mM) (2) Lack of inhibition by substrate

35
Q

signalling pathway within Bcells

A

Glut2 senses high conc of glucose 1) Glucose is converted to glucose-6-p by glucokinase 2) G-6-P is converted to F-6-P 3) to pyruvate 4) to acetyl-CoA 5) to cholesterol, fatty acids etc

36
Q

processing of insulin within beta cells

A

insulin is synthesises as a preproinsulin in the ribosome of the RER. Preproinsulin is then cleaved to proinsulin, which is transported to the Golgi apparatus where is it packaged into secretory granules located close to the cell membrane

37
Q

proinsulin is cleaved into

A

proinsulin is cleaved into equimolar amount son insulin and C peptide in the secure granules

38
Q

what is insulin packaged into

A

secretory granules

39
Q

where are secretory granules located

A

close to the membrane to allow rapid release

40
Q

processing of insulin within beta cells (easy)

A

1) preproinsuline is cleaved to proinsulin
2) proinsulin is cleaved to insulin and c-peptide in equal amounts

this is why C-peptide is a marker of insulin

41
Q

Insulin secretion from B cells

A

1) unactivated b cell will have open K+ channels
2) when GLUT2 senses a high enough BP, it opens and allows the influx of glucose
3) glucose is converetd to glucose 6 phosphate by glucokinase
4) glucokinase is further metabolised to produce ATP
5) ATP causes K+ channels to close
6) this depolarises the membrane (becomes more negative)
7) stimulates the influx of calcium
8) calcium causes insuli secretry granules to fuse withteh cell membrane

(1-5) Translational Medical Science (26 decks)

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