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Semester 2 - MEH > 13. The endocrine pancreas > Flashcards

13. The endocrine pancreas Flashcards

1
Q

What three regions is the developing GI tract divided into?

A

Foregut: supplied by blood from the coeliac trunk
Midgut: supplied by the SMA (superior mesenteric artery)
Hindgut: supplied by the IMA (inferior mesenteric artery)

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2
Q

What does the pancrease develop from embryonically?

A

Outgrowth of the foregut - so pancreas gets blood supply from coeliac trunk

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3
Q

where is the pancrease

A

Back of abdomen behind stomach the right side

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4
Q

What are the functions of the pancreas?

A

1) Exocrine function : produces digestive enzymes secreted directly into duodenum
- Exocrine function forms the bulk of the gland
- Alkaline secretions via pancreatic duct to duodenum

2) Endocrine function: hormone production
• From Islets of Langerhans in close proximity to a blood supply
• ~ 1% endocrine tissue, 99% exocrine tissue

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5
Q

What are important polypeptide hormones secreted by the pancreas? What types of cells are they produced by?

A
  • Insulin (beta cells)
  • Glucagon (alpha cells)
  • Somatostatin (delta cells)
  • Pancreatic polypeptide (PP cells)
  • Gastin (G cells)
  • Ghrelin (e cells)
  • Vasoactive intestinal peptide (VIP cells)
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6
Q

What does insulin and glucagon regulate?

A

Metabolism of carbohydrates, proteins and fats (glucose regulation)

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7
Q

What does insulin do?

A

lowers blood glucose levels

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8
Q

What does glucagon do?

A

raises blood glucose levels

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9
Q

What is insulin signalled by?

A

Feeding

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10
Q

hat is glucagon signalled by?

A

Fasting

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11
Q

What tissues does insulin target?

A

Liver, adipose, skeletal muscle

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12
Q

What tissues does glucagon target?

A

Liver, adipose

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13
Q

What organ uses glucose at the fastest rate?

A

Brain - relies on a controlled circulation of glucose as sensitive rises (increases osmolarity means fluid moves out of brain cells and they shrink) and falls

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14
Q

What is the normal range of plasma glucose?

A

3.3-6 mol/L

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15
Q

What is the usual range of plasma glucose after a meal

A

7-8 mmol/L

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16
Q

What is the renal threshold of plasma glucose?

A

10 mmol/L

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17
Q

What is glycosuria?

A

presence of glucose in the urine - renal threshold exceeded

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18
Q

How does the renal threshold of pregnant women change?

A

Lower than usual,so glucose in the urine not a cause for concern

19
Q

How does the renal threshold of the elderly change?

A

Increases - glycosuria is a concern

20
Q

How are insulin and glucagon carried?

A

Water soluble so dissolve in plasma - no special transport proteins

21
Q

What is the half life of insulin and glucagon?

A

5 min

22
Q

How are insulin and glucagon inactivated?

A

Receptor with hormone bound can be internalised

23
Q

How is insulin synthesised?

A
  • Pre pro insulin - long polypeptide chain
  • Cleavage to pro insulin which folds to ensure that there is correct alignment of the cysteine residues and the correct disulphide bonds form
  • Pro insulin leaves the ER in a golgi vesicle
  • Moves through Golgi apparatus to be cleaved again into two polypeptide chains (C peptide and insulin)
  • both chains marginate in vesicles to the cell surface
  • waits for signal to be released by exocytosis
24
Q

What is the ratio of insulin and c protein in the secretory protein?

A

As C-peptide is released with insulin in equimolar amounts, its level in plasma is a useful marker of endogenous insulin release. Measurement of plasma C peptide levels in patients receiving insulin can be used to monitor any endogenous insulin secretion.

25
Q

What is the structure of insulin?

A
  • 2 chains: α and β chain
  • linked covalently by 2 disulphide bonds
  • third intra-chain disulphide bond within the α chain
26
Q

What type of receptor is the insulin receptor?

A

Tyrosine kinase receptor

- already exits as a dimer rather than forming dimer after ligand binding (like in other tyrosine kinase receptors)

27
Q

Other than its effects on its main target tissues, what is insulin also required for?

A

Normal growth and development of most tissues of the body

28
Q

What type of metabolism are the effects of insulin?

A

Anabolic

- clearing absorbed nutrients (following a meal)

29
Q

How quick are most of the effects of insulin and what do they produce changes in?

A

Most of the effects occur rapidly (sec/hr)

Changes in the activities of pre-existing functional proteins such as enzymes and transport molecules in target tissues

30
Q

What are the effects of insulin on carbohydrates?

A
  • Increase glucose transport into adipose tissue & skeletal muscle.
  • Increase glycogenesis and decrease glycogenolysis in liver & muscle.
  • Decrease gluconeogenesis in liver.
  • Increase glycolysis in liver & adipose tissue.
31
Q

What are the effects of insulin on lipids?

A
  • Decrease lipolysis in adipose tissue.
  • Increase lipogenesis and esterification of fatty acids in liver & adipose tissue.
  • Decrease ketogenesis in liver.
  • Increase lipoprotein lipase (transport of fatty acids from lipoproteins into adipocytes) activity in the capillary bed of tissues such as adipose tissue.
32
Q

What are the effects of insulin on amino acids/protein?

A
  • Increase amino acid uptake and protein synthesis in liver, muscle & adipose tissue.
  • Decrease proteolysis in liver, skeletal muscle & heart muscle.
33
Q

What factors control insulin secretion?

A
  • metabolites (glucose, amino acids, fatty acids)
  • GI tract hormones (gastrin, secretin, cholecystokinin)
  • neurotransmitters (adrenaline, noradrenaline, acetyl choline)
34
Q

Which of the factors that control insulin secretion inhibit and stimulate secretion?

A

Adrenaline and noradrenaline inhibit secretion

- the other stimulate secretion

35
Q

How is insulin released?

A

ATP generated by glucose metabolism closes ATP sensitive K+ channels (inwardly rectifying) and depolarises β cell membrane –> opens voltage gated Ca++ channels. Ca++ influx stimulates insulin secretion.
- calcium triggers insulin containing vesicles to be released by exocytosis

36
Q

How does low metabolism affect insulin secretion?

A
  • when metabolism is low, potassium ATP channels open so potassium can leave
  • membrane doesn’t become depolarised
  • no insulin is secreted
37
Q

What is the structure of glucagon?

A
  • single chain
  • 29 amino acid peptide hormone
  • no disulphide bonds
  • flexible 3D structure (takes active form after binding to its receptor)
38
Q

How is glucagon synthesised?

A

Preproglucagon processed in the RER and Golgi and secreted

39
Q

Which glucose transporter is the primary transporter of glucose in pancreatic beta cells?

A

GLUT2 - allows glucose entry that ultimately regulates insulin synthesis and release by causing an increase in ATP concentration

40
Q

What are the major actions of glucagon?

A
  • Increase glycogenolysis and decrease glycogenesis in liver.
  • Increase gluconeogenesis in liver.
  • Increase ketogenesis in liver.
  • Increase lipolysis in adipose tissue.
41
Q

What type of receptor is the glucagon receptor?

A

G-protein coupled receptor

42
Q

What is the effect of of glucagon binding to its receptor?

A

activates the enzyme adenylate cyclase, which increases cyclic AMP (cAMP) intracellularly. High levels of cAMP activate protein kinase A (PKA), which phosphorylates and thereby activates a number of important enzymes in target cells

43
Q

What factors affect glucagon secretion?

A

Decrease in the blood glucose concentration increases the rate of glucagon secretion

Secretion is inhibited by insulin and an increase in blood glucose concentration.

44
Q

Summarise the actions of insulin

A
  • in the liver it increases glycogen synthesis by stimulating glycogen formation and by inhibiting breakdown
  • in muscles it increase uptake of AA promoting protein synthesis
  • in liver inhibits breakdown of AA
  • in adipose tissue increases the storage of triglycerides

Semester 2 - MEH (23 decks)

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