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TMS > Trigger 1: Insulin secretion > Flashcards

Trigger 1: Insulin secretion Flashcards

1
Q

What is blood Glucose control?

A

Action of insulin and glucagon to maintain blood glucose levels

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2
Q

Normal blood glucose

A

usually constant between 4-7mmol/l glucose in blood

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3
Q

When is blood glucose highest

A

after food

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4
Q

factors that affect BG

A

-exercise -food -illness -stress

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5
Q

Insulin

A

Insulin acts quickly + can respond to changes in blood glucose levels to return to normal!

Insulin - decreases blood sugar levels to normal range.

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6
Q

Action of insulin

A

Insulin is 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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7
Q

Glucagon

A

increases blood sugar level

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8
Q

Action of 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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9
Q

receptor for glucagon is a

A

GPCR found on liver, increases cAMP and PKA

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10
Q

Where are insulin and glucagon produced?

A

Pancreas

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11
Q

The role of the pancreas

A
  • Pancreas sits below the stomach
  • Pancreas is connected to duodenum
  • Main role of pancreas is to produce enzymes from exocrine (released to exterior) part of the pancreas (involved with digestion) so secreted to duodenum
  • 1% of pancreas = endocrine (islets of Langerhans)
    • contain Beta cells = insulin
    • alpha cells = glucagon
  • secrete endocrine hormones - releases within the body (into blood stream)
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12
Q

Beta cells

A

Secrete insulin- decrease BG

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13
Q

Alpha cells

A

Secrete glucagon- increase BG

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14
Q

Islet of Langerhans

A
  • Halo of alpha cells around the outside (glucagon producing)
  • Beta cells packed in the middle (insulin producing)
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15
Q

Human islets

A
  • More interaction between the 2 type of cells
  • Alpha cells throughout islet, not just in the exterior
  • Close interaction between both cell types
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16
Q

Regulation of blood glucose - what tissues does insulin work on?

A
  • fat= lipolysis,
  • liver= glucose production,
  • muscle= glucose uptake
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17
Q

Regulation of blood glucose - glucagon - what tissues does it work on?

A

liver

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18
Q

When BG is high

A

1) beta cells of pancreas of islets of LAngerhans stimulated to release insulin into blood 2) Insulin works on 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

More detail

Insulin works on peripheral tissues (liver, skeletal muscle + adipose which have receptors to respond to insulin. Insulin promotes different processes to help with uptake and storage of glucose (and fat uptake also). Liver = insulin can act on liver to help store glucose as glycogen. It can also decrease glucose production. Decrease Gluconeogenesis – produce glucose from other components (new). Insulin stops Gluconeogenesis – allow glucose to be stored + reduce amount of free glucose). Adipose and muscle  Insulin promote glucose uptake from blood stream here. Insulin can have effect on fat storage and uptake – inhibits lipolysis so promotes fat storage. All these actions, uptake new glucose from blood and blood glucose levels fall back to normal

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19
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

More detail

  • Pancreas alpha cells secretes Glucagon
  • Glucagon mainly acts on the Liver
    • Act to promote glycogen breakdown (break down stores of glucose)
    • Promotes gluconeogenesis (production of glucose)
    • Free glucose then released in the blood stream and allows the blood glucose levels to rise
  • Skeletal muscle
    • Store glycogen – can break it down to have glucose for energy
    • Skeletal muscle can’t release glucose back into the blood stream
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20
Q

How many GLUT transporters

A

14 main

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21
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

22
Q

GLUT 2

A

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

23
Q

GLUT 3

A

o Brain o Higher affinity for glucose than other GLUTs

24
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

25
Q

GLUT 5

A

o Intestinal tissue, kidney and spermatozoa o Fructose transporter

26
Q

Which GLUT is activated during the insulin signalling pathway

A

GLUT 4

27
Q

which GLUT signals for B cells to release insulin

A

GLUT2

28
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

29
Q

insulin acts on

A

muscle, adipose and liver

30
Q

response to insulin has how many phases

A

2

31
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

32
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

33
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

34
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

35
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

36
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
37
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

38
Q

Sympathetic

A

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

39
Q

Parasympathetic

A

stimulates insulin secretion by stimulating Ach

40
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

41
Q

Glucokinase

A

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

42
Q

glucokinase is a key componenet of

A

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

43
Q

characteristics of glucokinase

A

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

44
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

45
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

46
Q

proinsulin is cleaved into

A

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

47
Q

what is insulin packaged into

A

secretory granules

48
Q

where are secretory granules located

A

close to the membrane to allow rapid release

49
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

50
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

TMS (2 decks)

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