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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?

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
What is the structure of insulin?
- 2 chains: α and β chain - linked covalently by 2 disulphide bonds - third intra-chain disulphide bond within the α chain
26
What type of receptor is the insulin receptor?
Tyrosine kinase receptor | - already exits as a dimer rather than forming dimer after ligand binding (like in other tyrosine kinase receptors)
27
Other than its effects on its main target tissues, what is insulin also required for?
Normal growth and development of most tissues of the body
28
What type of metabolism are the effects of insulin?
Anabolic | - clearing absorbed nutrients (following a meal)
29
How quick are most of the effects of insulin and what do they produce changes in?
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
What are the effects of insulin on carbohydrates?
* 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
What are the effects of insulin on lipids?
* 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
What are the effects of insulin on amino acids/protein?
* Increase amino acid uptake and protein synthesis in liver, muscle & adipose tissue. * Decrease proteolysis in liver, skeletal muscle & heart muscle.
33
What factors control insulin secretion?
- metabolites (glucose, amino acids, fatty acids) - GI tract hormones (gastrin, secretin, cholecystokinin) - neurotransmitters (adrenaline, noradrenaline, acetyl choline)
34
Which of the factors that control insulin secretion inhibit and stimulate secretion?
Adrenaline and noradrenaline inhibit secretion | - the other stimulate secretion
35
How is insulin released?
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
How does low metabolism affect insulin secretion?
- when metabolism is low, potassium ATP channels open so potassium can leave - membrane doesn't become depolarised - no insulin is secreted
37
What is the structure of glucagon?
- single chain - 29 amino acid peptide hormone - no disulphide bonds - flexible 3D structure (takes active form after binding to its receptor)
38
How is glucagon synthesised?
Preproglucagon processed in the RER and Golgi and secreted
39
Which glucose transporter is the primary transporter of glucose in pancreatic beta cells?
GLUT2 - allows glucose entry that ultimately regulates insulin synthesis and release by causing an increase in ATP concentration
40
What are the major actions of glucagon?
* Increase glycogenolysis and decrease glycogenesis in liver. * Increase gluconeogenesis in liver. * Increase ketogenesis in liver. * Increase lipolysis in adipose tissue.
41
What type of receptor is the glucagon receptor?
G-protein coupled receptor
42
What is the effect of of glucagon binding to its receptor?
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
What factors affect glucagon secretion?
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
Summarise the actions of insulin
* 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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