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END 207: Physiology > Pancreas Intro + insulin > Flashcards

Pancreas Intro + insulin Flashcards

1
Q

Cells secreting Pancreatic polypeptide

A

F cells

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2
Q

Cells secreting Glucagon

A

A cells

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3
Q

Cells secreting somatostatin

A

D cells

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4
Q

Cells secreting insulin

A

B cells

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5
Q

Chemistry of Insulin

A

Polypeptide enzyme with 2 chains of amino acids linked by disulfide bridges

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6
Q

Halflife of insulin

A

5 minutes

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7
Q

Normal level of insulin in urine

A

Little to none

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8
Q

Describe the transport & Breakdown of insulin

A
  • Insulin circulates in the plasma in free form only
  • When it binds to receptor of cells, it is internalized by Receptor mediated endocytosis
  • It is then destroyed in the cell by Insulinaze enzyme
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9
Q

Explain why IGF-1 & IGF-2 do not fix DM after pancreatectomy

A

even though the act on same receptor as insulin, and are not supressed by specific anti-insulin antibodies, their effect is very weak compared to insulin

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10
Q

Describe structure of Insulin receptor

A

Tetramer (4 subunits):
* 2 alpha: outside cell membrane
* 2 Beta: intracytoplasmic

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11
Q

Mechanism of action of Insulin

A
  1. the 2 intracytoplasmic Beta subunits possess tyrosine kinase activity
  2. it causes autophosphorylation when insulin binds (activation)
  3. active tyrosine kinase then phosphorylate Insulin receptors Substrates (IRS 1,2,3,4)
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12
Q

When does number of Insulin rececptors decrease

A

obesity & Acromegaly –> High insulin level (as down regulation)

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13
Q

When does number of Insulin rececptors Increase

A

In starvation —> prolonged low insulin levels (up regulation)

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14
Q

When does affinity of Insulin rececptors decrease

A

excess Glucocorticoids (cortisol decreases Peripheral glucose utilisation)

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15
Q

When does Affinity of Insulin rececptors Increase

A
  • Adrenal insufficiency
  • Starvation
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16
Q

Describe the cellular activity of insulin depending on time & site of binding

A

Rapid effect (seconds): increases permiability of the cell to:
* glucose
* Amino Acids
* Potassium
* Phosphate

Intermidiate effect (minutes):
* Phosphorylation & dephosphrylation of metabolic enzymes in the cell

Delayed effect (hours):
* Change in rate of transcription & Translation
* Change rate of DNA synthesis

17
Q

Action of Insulin on Carbohydrate metabolism

A

reduces blood glucose to maintain it:
On Muscles:
* Translocation of endosomes containing GLUT4 to cell membrane
* Decreases utilisation of fat as source of energy

On Liver:
* Increases Phosphorylation of glucose into G6P, thus maintaining a concentration gradient & increasing uptake of glucose by liver
* Stimulates glycogenesis
* Inhibits glycogenolysis
* Inhibits gluconeogenesis

On Adipose tissue:
* Increases Number of GLUT4 –> increases Uptake of adipose tissue for glucose –> glycerol

18
Q

Explain how Exercise can help in DM

A
  • Exercise acitvates 5’ AMP Kinase
  • It stimulates translocation of GLUT4 Endosomes to cell membrane (like insulin)
19
Q

True or false, insulin increases GLUT 2 on cell membrane

A

False, GLUT 2 (in liver) is insulin insensitive

20
Q

True or false, insulin increases GLUT 4 on cell membrane

A

True, in Muscles and adipose tissue

21
Q

Sites where insulin doesnt increase glucose uptake

A
  • RBCs
  • Brain neurones
  • Renal tubules
  • Intestinal mucosa
22
Q

Action of Insulin on Fat metabolism

A
  • Fat sparing: decreases utilisation of fat as energy source
  • Lipogenic (excess glucose –> FFA)
  • Inhibits lipolysis
  • stimulates use of Ketoacids by peripheral tissue (Antiketogenic)
23
Q

Action of Insulin on Protein metabolism

A

Anabolic:
* Increases uptake of AA
* increases Transcription & translation
* Inhibits protein catabolism (& gluconeogenisis)

24
Q

Action of Insulin on Growth

A
  • Direct: synthesis of macromolecules for cartilage & bones
  • Indirect: increases transcription of IGF-1, & inhibits transcription of IGF-1 binding protein so it stays in free active form
25
Q

Relation between Potassium & Insulin

A
  • Insulin can be clincally used in renal failure associated with Hyperkalemia: It increases Na+K+ pump, therefore increasing intracellular potassium and decreasing plasma potassium
  • Hypokalemia decreases insulin secretion: such as in primary hyperaldosteronism
26
Q

Explain why thiazide diuretics is not advised in DM

A

It increases Potassium excretion —> Hypokalemia
* Hypokalemia affects insulin secretion –> worsens DM

27
Q

Explain how food glucose causes secretion of Insulin

A
  1. After meal, glucose enters pancreatic B cells through GLUT2
  2. Glucose is oxidised to give ATP
  3. ATP closes ATP sensitive K+ Channels
  4. This decreases K+ efflux
  5. K+ accumulates intracellular & causes depolarization
  6. Depolarization opens Voltage gated Ca2+ channels
  7. Ca2+ influx
  8. Causes exocytosis of Insulin
28
Q

Factors increasing/stimulating insulin secretion

A

food:
* Glucose
* Amino acids (especially Arginine & Lysine)

Hormones:
* GIP
* Gastrin
* Secretin
* CCK
* Glucagon

others:
* Parasympathetic innervation
* Beta adrenergic activation
* cAMP

29
Q

Factors inhibiting Insulin secretion

A
  • Somatostatin
  • Insulin itself (negative feedback)
  • Leptin
  • (Alpha2) sympathetic innervation
30
Q

Describe how other non GIT & pancreatic hormone influence Insulin secretion

A
  • May cause hyperplasia of B cells–> More insulin
  • may decrease insulin action on peripheral tissue (cortisol)
  • May exhaust B cells

END 207: Physiology (20 decks)

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