Endocrine Pancreas

Question 1

Where is the pancreas?

Answer 1

In Abdomen behind stomach

Question 2

What kind of gland is the pancreas?

Answer 2

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

Question 3

Functions of pancreas

Answer 3

Digestive and endocrine

Question 4

Anatomy of pancreas (H and E)

Answer 4

Acini (bunched grapes)
Ducts
Islets of Langerhans

Question 5

Which cells are responsible for exocrine function of the pancreas?

Answer 5

Acinar cells/Acini

Question 6

Which cells are responsible for endocrine function of the pancreas?

Answer 6

Islets of Langerhans

Question 7

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

Answer 7

Alpha - glucagon
Beta - insulin
Delta - somatostatin

Question 8

Describe the features of insulin and glucagon (4)

Answer 8

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

Question 9

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

Answer 9

Insulin dominates in FED state (hormone of plenty)

Lowers plasma glucose

Question 10

Insulin actions (4)

Answer 10

• Increase glucose oxidation
• Increase glycogen synthesis
• Increase fat synthesis
• Increase protein synthesis

Question 11

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

Answer 11

Anabolic:
Liver
Adipose
Skeletal muscle

Question 12

What does insulin do in adipose and skeletal muscle?

Answer 12

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

Question 13

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

Answer 13

Dominates in fasted state

Raises plasma glucose

Question 14

Glucagon actions

Answer 14

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

Question 15

What can glucagon act on?

Answer 15

Catabolic:
Liver
Adipose tissue

Question 16

What can glucagon not act on?

Answer 16

Skeletal muscle - lacks glucagon receptors

Question 17

Insulin structure

Answer 17

Peptide hormone

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

Question 18

How is insulin stored?

Answer 18

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

Question 19

Insulin synthesis steps

Answer 19

DNA in beta cell

mRNA
(translation)

Preproinsulin
(signal peptide cleavage)

Proinsulin
(proteolytic processing)

Insulin + C peptide

Question 20

Function of signal sequence

Answer 20

Direct preproinsulin to ER

Question 21

Where does proinsulin then go for processing?

Answer 21

Golgi

Question 22

proinsulin structure

Answer 22

Insulin + C peptide

Prohormone convertase 1 and 2

Question 23

Function of C peptide

Answer 23

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

Question 24

What cleaves ends of insulin and C peptides apart?

Answer 24

Carboxypeptidase H

Question 25

Explain stimulation of insulin secretion:

Answer 25

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)

Question 26

Stimulators of insulin release

Answer 26

High plasma glucose, amino acids or free fatty acids | Parasympathetic nervous system

Question 27

Inhibitors of insulin release

Answer 27

Low plasma glucose, amino acids or free fatty acids | Sympathetic nervous system

Question 28

Hormones stimulating insulin

Answer 28

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

Question 29

Hormones inhibiting insulin release

Answer 29

Somatostatin Leptin Adrenaline (at alpha cell receptor)

Question 30

Insulin secretion is

Answer 30

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

Question 31

when is no insulin produced?

Answer 31

When plasma glucose is below 2.8mmol/L

Question 32

Half maximal insulin response is at

Answer 32

8mmol/L | Maximum is at 16mmol/L

Question 33

How does insulin work on receptor?

Answer 33

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

Question 34

3 main target tissues and actions insulin (activation)

Answer 34

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

Question 35

3 main target tissues and actions insulin (inhibits)

Answer 35

INHIBITS Liver - gluconeogenesis, glycogenolysis, lipolysis Muscle - lipolysis, protein catabolism Fat - lipolysis

Question 36

Glucagon structure

Answer 36

Peptide hormone No disulphide bonds Produced by pancreatic alpha cells

Question 37

What does glucagon do

Answer 37

Opposes insulin MAIN TARGET = liver (gluconeogenesis, glycogenolysis) Stimulates lipolysis in adipose

Question 38

Glucagon synthesis

Answer 38

DNA (transcription) mRNA (translation) Preproglucagon (signal peptide cleavage) Proglucagon (proteolytic processing) Glucagon

Question 39

Proglucagon structure

Answer 39

Complex | Contains several peptide hormones

Question 40

How is glucagon release controlled?

Answer 40

``` 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 ```

Question 41

How does glucagon act on receptor?

Answer 41

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

Question 42

What enzymes does glucagon activate/inhibit?

Answer 42

Activates: Glycogen phosphorylase Inhibits: Glycogen synthase

Question 43

What does GaS glucagon receptor do?

Answer 43

cAMP levels rise Activation of PKA Phosphorylation of PPK

Question 44

Diabetes mellitus

Answer 44

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

Question 45

Type 1 diabetes mellitus

Answer 45

Absolute insulin deficiency | Autoimmune destruction of pancreatic beta cells

Question 46

Type 2 diabetes mellitus

Answer 46

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