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MEH 2023 > Endocrine Pancreas > Flashcards

Endocrine Pancreas Flashcards

1
Q

Where is the pancreas?

A

In Abdomen behind stomach

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2
Q

What kind of gland is the pancreas?

A

Heterocrine gland with exocrine cells (99%) endocrine (1%) cells

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3
Q

Functions of pancreas

A

Digestive and endocrine

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4
Q

Anatomy of pancreas (H and E)

A

Acini (bunched grapes)
Ducts
Islets of Langerhans

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5
Q

Which cells are responsible for exocrine function of the pancreas?

A

Acinar cells/Acini

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6
Q

Which cells are responsible for endocrine function of the pancreas?

A

Islets of Langerhans

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7
Q

Name the major types of cells in islets and what each one secretes

A

Alpha - glucagon
Beta - insulin
Delta - somatostatin

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8
Q

Describe the features of insulin and glucagon (4)

A
  • Both peptide hormones (water soluble)
  • Both have short half life (about 5 mins)
  • Insulin receptor = Tyrosine kinase
  • Glucagon receptor = GPCR
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9
Q

Which hormone dominates in the FED state and what does this hormone act to do?

A

Insulin dominates in FED state (hormone of plenty)

Lowers plasma glucose

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10
Q

Insulin actions (4)

A
  • Increase glucose oxidation
  • Increase glycogen synthesis
  • Increase fat synthesis
  • Increase protein synthesis
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11
Q

What kind of actions does insulin have? What tissues can insulin act on? (3)

A

Anabolic:
Liver
Adipose
Skeletal muscle

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12
Q

What does insulin do in adipose and skeletal muscle?

A
  • Promotes translocation of GLUT4 to membrane in adipose and skeletal muscle
  • This promotes glucose uptake by these tissues
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13
Q

Which state does glucagon dominate in, and what does it aim to do?

A

Dominates in fasted state

Raises plasma glucose

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14
Q

Glucagon actions

A

Increase gluconeogenesis (glucose production)
Increase glycogenolysis (glycogen brekadown)
Increase ketogenesis (production of ketone bodies)

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15
Q

What can glucagon act on?

A

Catabolic:
Liver
Adipose tissue

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16
Q

What can glucagon not act on?

A

Skeletal muscle - lacks glucagon receptors

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17
Q

Insulin structure

A

Peptide hormone

2 chains - A and B chains held by disulphide bonds (3rd intrachain)

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18
Q

How is insulin stored?

A

As a hexamer held together by zinc ion coordinated by histadines
Hexamer = highly stable, protects insulin

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19
Q

Insulin synthesis steps

A

DNA in beta cell

mRNA
(translation)

Preproinsulin
(signal peptide cleavage)

Proinsulin
(proteolytic processing)

Insulin + C peptide

20
Q

Function of signal sequence

A

Direct preproinsulin to ER

21
Q

Where does proinsulin then go for processing?

A

Golgi

22
Q

proinsulin structure

A

Insulin + C peptide

Prohormone convertase 1 and 2

23
Q

Function of C peptide

A

Clinical marker for insulin produced by pancreas (man-made has no C peptide)

24
Q

What cleaves ends of insulin and C peptides apart?

A

Carboxypeptidase H

25
Q

Explain stimulation of insulin secretion:

A

Increase glucose = increase glycolysis = increase ATP
High ATP closes ATP sensitive K+ channels
Membrane becomes depolarised
V gated Ca2+ channels open allowing Ca2+ into cell
Causes insulin to migrate to membrane and be released from vesicles (exocytosis)

26
Q

Stimulators of insulin release

A

High plasma glucose, amino acids or free fatty acids

Parasympathetic nervous system

27
Q

Inhibitors of insulin release

A

Low plasma glucose, amino acids or free fatty acids

Sympathetic nervous system

28
Q

Hormones stimulating insulin

A

Glucagon
Gastroinhibitory peptide (GIP)
Gastrin
Adrenaline (at beta cell receptor)

29
Q

Hormones inhibiting insulin release

A

Somatostatin
Leptin
Adrenaline (at alpha cell receptor)

30
Q

Insulin secretion is

A 
Biphasic
Initial burst (5-15 mins)
Second phase (gradual, lasts as long as glucose is high)
31
Q

when is no insulin produced?

A

When plasma glucose is below 2.8mmol/L

32
Q

Half maximal insulin response is at

A

8mmol/L

Maximum is at 16mmol/L

33
Q

How does insulin work on receptor?

A

Insulin binds to tyrosine kinase receptor
Receptor auto-phosphorylation
Activation of signalling complexes at membrane

34
Q

3 main target tissues and actions insulin (activation)

A

ACTIVATES:
Liver - glycogenesis, lipogenesis, glycolysis

Muscle - glucose uptake (GLUT4), lipogenesis, glycogenesis, glycolysis, protein synthesis, amino acid transport

Adipose - glucose uptake (GLUT4), lipogenesis, glycolysis

35
Q

3 main target tissues and actions insulin (inhibits)

A

INHIBITS
Liver - gluconeogenesis, glycogenolysis, lipolysis

Muscle - lipolysis, protein catabolism

Fat - lipolysis

36
Q

Glucagon structure

A

Peptide hormone
No disulphide bonds
Produced by pancreatic alpha cells

37
Q

What does glucagon do

A

Opposes insulin
MAIN TARGET = liver (gluconeogenesis, glycogenolysis)

Stimulates lipolysis in adipose

38
Q

Glucagon synthesis

A

DNA
(transcription)

mRNA
(translation)

Preproglucagon
(signal peptide cleavage)

Proglucagon
(proteolytic processing)

Glucagon

39
Q

Proglucagon structure

A

Complex

Contains several peptide hormones

40
Q

How is glucagon release controlled?

A 
In alpha cells:
Low glucose = low ATP 
ATP sensitive K+ channels CLOSE (in response to low ATP this time)
Depolarisation of cell
Voltage gated Ca2+ channels open
Triggers exocytosis of glucagon
41
Q

How does glucagon act on receptor?

A

Glucagon binds to GPCR (G alpha S)
G protein = activated
Effector protein = activated
2nd messenger formed

42
Q

What enzymes does glucagon activate/inhibit?

A

Activates: Glycogen phosphorylase
Inhibits: Glycogen synthase

43
Q

What does GaS glucagon receptor do?

A

cAMP levels rise
Activation of PKA
Phosphorylation of PPK

44
Q

Diabetes mellitus

A

Chronic hyperglycaemia

Renal threshold for glucose is exceeded so glucose appears in urine (glucosuria)

45
Q

Type 1 diabetes mellitus

A

Absolute insulin deficiency

Autoimmune destruction of pancreatic beta cells

46
Q

Type 2 diabetes mellitus

A

Relative insulin deficiency
Insulin resistance - cells respond less well to insulin
B cells wear out from over production

MEH 2023 (8 decks)

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