Lecture 19: Endocrine pancreas Flashcards

1
Q

Describe the pancreas’ function

A

Pancreas is an organ in the digestive and endocrine system. It also acts as an exocrine and endocrine gland.

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2
Q

Describe the anatomy of the pancreas

A

Pancreas made up of exocrine acinar cells and endocrine islets of Langerhans.

Former secretes digestive enzymes.
Latter consists of mainly α, β & δ cells which.

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3
Q

Describe the structure & function of pancreatic exocrine tissue.

A

Acini: grape-like acinar cells that secrete digestive enzymes.

Ductal cells: branches that link the acini that secrete bicarbonate which buffers stomach gastric acid; creates optimum pH environment for the digestive enzymes.

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4
Q

There are a number of different digestive enzymes that the body produces.

Name 3 digestive enzymes secreted by the pancreas.

A

Proteases: trypsin + chymotrypsin

Pancreatic lipase: digest TAGs

Pancreatic amylase: digest starch –> glucose

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5
Q

Why doesn’t trypsin and chymotrypsin digest the pancreas itself?

A

Trypsin and chymotrypsin are stored as pro-enzymes (trypsinogen and chymotrypsinogen) instead of its active form so that prevents the pancreas digesting itself.

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6
Q

Aside from pro-enzymes, what other methods control the pancreas the activity of trypsin & chymotrypsin?

A

Acini secrete a trypsin inhibitor to prevent the enzyme from digesting the pancreas.

Enteropeptidases are SI enzymes that activate trypsinogen to trypsin by cleaving the proenzyme. This causes trypsin to do the same to chymotrypsinogen –> chymotrypsin.

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7
Q

What are the 3 major endocrine cells of the islets of Langerhans and their secretions?

A

α - glucagon
β - insulin
δ - somatostatin

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8
Q

What are the 3 minor endocrine cells of the islets of Langerhans and their secretions?

A

PP cells - PP (pancreatic peptides)
ε - ghrelin
G - gastin

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9
Q

In a micrograph, what can you do to identify the cells of in an islet of Langerhans?

A

You can stain the islet of Langerhans with the cell secretions’ respected antibodies…

  • α cell is stained with glucagon Ab.
  • β cell is stained with insulin Ab etc…
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10
Q

Compare and contrast insulin & glucagon.

A

Both are peptide hormones.
Both have a short half life.
Both affect liver processes.
Both act in response to plasma [glucose].

-I receptor = tyrosine kinase family
G receptor = GPCR family

-I dominates in fed state
G dominates in fasted state

-I causes anabolic reactions
G causes catabolic reactions

-I affects liver, MSK and adipose
G affects all of the above but MSK

-I causes decrease plasma [glucose]
G causes increase plasma [glucose]

-I has disulphide bonds
G doesn’t

-I secreted by β cells
G secreted by α cells

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11
Q

Describe the structure of insulin and how the structure maintains stability.

A

Insulin is made from 1α & 1β chain connected by 2 inter- chain disulphide bonds.
There is 1 intra-chain disulphide bond within the α chain. All these bonds are between cysteine residues.

Insulin is stored as a hexamer which is held together by a Zn ion. This creates stability.

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12
Q

Briefly give a description of insulin synthesis.

A
  1. DNA in β cell transcribed.
  2. mRNA is translated into peptide chain (preproinsulin)
  3. Enzymes cleave the signal sequence (pre-) creating inactive proinsulin.
  4. Proinsulin passes into golgi.
  5. When needed, secretory vesicles (with proinsulin) bind to membrane.
  6. Vesicle enzymes chop proinsulin into insulin and C-peptide.
  7. Insulin and C-peptide get secreted into the bloodstream.
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13
Q

Why is C-peptide clinically important?

A

C-peptide is a clinical marker for pancreatic insulin secretion. C-peptide remains in blood much longer than insulin so easily assayed for levels of pancreatic insulin secretion.

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14
Q

Describe how the β cells are activated when in a fed state.

A
  1. Fed state = high glucose levels
  2. Glucose enters glycolysis, TCA cycle, Ox. phosph.
  3. More ATP synthesised
  4. More ATP closes K-ATP channel
  5. Less K+ leave the cell
  6. Cell potential difference increases = depolarisation
  7. V-G Ca2+ channels open and influx into β cell
  8. Influx of Ca2+ triggers exocytosis and insulin is secreted.
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15
Q

Can you think of any factors that stimulate insulin secretin?

A

High plasma glucose
High plasma FA
High plasma AA

Too much glucagon (need balance)
Gastrin
Secretin
Adrenaline (at β receptor)

PARASYMPATHETIC SYSTEM

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16
Q

Can you think of any factors that inhibit insulin secretion?

A

Low plasma glucose
Low plasma FA
Low plasma AA

Somatostatin
Leptin
Adrenaline (at α receptor)

SYMPATHETIC SYSTEM

17
Q

What does biphasic mean and how does it apply to insulin?

A

Biphasic means in 2 phases/ happens twice.

The initial insulin secretion is a quick burst that lasts 5-15mins.
The 2nd phase is a gradual increase in secretion that lasts as long as the plasma [glucose] remains >5mM.

18
Q

How much insulin is secreted when…

  • plasma [glucose] <2.8mmol/L
  • plasma [glucose] ~ 8mmol/L
  • plasma [glucose] ~ 16mmol/L
A

No insulin when plasma [glucose]<2.8mM

Half-maximal insulin when plasma [glucose] ~8mM

Maximum response when plasma [glucose]~16mM

19
Q

How does insulin exert its effect on cells?

A
  • Insulin binds to complementary tyrosine kinase receptor.
  • Receptor autophosphorylates
  • Signalling complexes are gathered and activated at the receptor (cell mem)
  • Effects on metabolic pathways & glucose uptake
20
Q

Insulin acts on 3 main target tissues. Which tissues are they?

A

Liver, Adipose, MSK

21
Q

How does insulin affect the liver?

A

Activates…

  • glycogenesis
  • lipogenesis
  • glycolysis

Inhibits…

  • glycogenolysis
  • lipolysis
  • gluconeogenesis
22
Q

How does insulin affect the MSK?

A

Activates…

  • Glucose uptake
  • Lipogenesis
  • Glycogenesis
  • Glycolysis
  • Protein synthesis
  • AA transport

Inhibits…

  • Lipolysis
  • Protein catabolism
23
Q

How does insulin affect adipose tissue?

A

Activates…

  • Glucose uptake
  • Lipogenesis
  • Glycolysis

Inhibits…
-Lipolysis

24
Q

How is glucagon synthesised?

A
  1. DNA transcribed in α cell.
  2. mRNA translated into peptide chain: preproglucagon.
  3. Enzymes clease signal sequence (pre-) leaving proglucagon.
  4. Proglucagon undergoes proteolytic processing.
  5. When needed, secretory enzymes will chop off the pro- part, leaving glucagon.
25
Q

How is glucagon release controlled?

A
  1. Fasted state = low plasma glucose
  2. Less glucose into glycolysis…ox. phosph.
  3. Less ATP syn.
  4. Low ATP levels close the K-ATP channels.
  5. Less K+ leaves α cell
  6. Potential difference inside cell increases = depolarises
  7. V-G Ca2+ channel open and influx into α cell.
  8. Influx of Ca2+ triggers exocytosis via vesicles = glucagon secretion.
26
Q

How does glucagon exert its effect on cells?

A
  • Target cells/tissues have complementary GPCR
  • G protein activated
  • Effector protein activated
  • 2° messenger formation
  • Effects on metabolic pathways & gene expression