Session 7- The Endocrine Pancreas

Question 1

What is acute chest syndrome

Answer 1

Vast-occlusive crisis

Microvasculature occlusion and bone marrow infarction

Secretory phospholase + pulmonary infection leads to acute chest syndrome

Hypoventilation resulting from rib and vertebral infarction

Question 2

Function of pancreas

Answer 2

Produce digestive enzymes secreted directly into duodenum- exocrine function which forms the bulk of the gland

Hormone production from islets of langerhans

Question 3

Staining of pancreas

Answer 3

Dark stain- exocrine tissue

Light pale blobs- islets of langerhands

Question 4

What is plasma glucose normally

Answer 4

3.3-6 mmol/L

Question 5

What is plasma glucose after a meal

Answer 5

7-8 mmol/L

Question 6

Renal threshold of plasma glucose

Answer 6

10 mmol/L

Question 7

When is glycosuria normal

Answer 7

Pregnancy

Elderly renal threshold increases

Question 8

What does insulin promote

Answer 8

Carbohydrate metabolism

Lipid metabolism

Protein metabolism

Insulin is anabolic, antigluconeogenic, anti-lipolitic, anti-ketotonic

Question 9

Insulin synthesis

Answer 9

1) pre-proinsulin is cleaved to produce proinsulin in RER
2) proinsulin is transported to Golgi
3) proinsulin is cleaved to produce insulin and C-peptide
4) secretory granule formation and exocytosis of insulin

Question 10

What does insulin consist of

Answer 10

2 unbranched peptide chains which are connected by 2 disulphide bridges that ensure stability

• 51 amino acids
• 2 polypeptide chains
• 2 disulphide bridges= rigid structure

Question 11

KATP Channels regulated by metabolism

Answer 11

Glucose closes kATP channels in pancreatic beta cells

Metabolic inhibition reopens kATP channels

Question 12

How does metabolism affect insulin secretion

Answer 12

Metabolism is low, KATP channels open, no insulin secreted

Metabolism high, KATP channels shut, insulin secreted

Question 13

What channels do glucose enter cells through and when

Answer 13

GLUT2 channels at 7mM

Question 14

How does ATP affect kATP channels

Answer 14

ATP inhibits the channel activity and reduced K+ efflux

This tiggers exocytosis of insulin

Question 15

What dos insulin do

Answer 15

Increases glucose uptake into target cells and glycogen synthesis via GLUT4 channel

Question 16

What does insulin do in the liver

Answer 16

It increases glycogen synthesis by stimulating glycogen formation and by inhibiting breakdown

Question 17

What does insulin do in muscles

Answer 17

Increases uptake of AA promoting protein synthesis

Inhibits breakdown of AA

Question 18

What does insulin do in adipose tissue

Answer 18

Increases the storage of triglycerides

Question 19

Structure of insulin receptor

Answer 19

Dimer

2 identical subunits spanning cell membrane

2 subunits are made of one alpha-chain and one beta-chain connected by a single di-sulphide bond

• alpha on exterior of membrane
• beta spans the cell membrane in a single segment

Question 20

Glucagon

Answer 20

• acts to raise blood glucose levels
• It is glycogenolytic,
• gluconeogeneic
• lipolytic
• ketogenic

Question 21

Margination

Answer 21

Movement of storage vesicles to cell surface

Question 22

Exoytosis

Answer 22

Fusion of vesicles membrane with plasma membrane with he release of the vesicles contents

Question 23

Effects of glucagon on liver

Answer 23

Increase rate of glycogen breakdown- glycogenolysis

Question 24

Effects of glucagon

Answer 24

• Gluconeogenic
• Stimulates lipolysis to increase plasma fatty acid
• glycogenolysis

Question 25

What are te potassium ATP channels like in insulin deficiency

Answer 25

``` mutations in the pore-forming Kir6.2 subunit or in the regulatory sulfonylurea receptor 1 (SUR1) subunit have been identified as the commonest cause of human neonatal diabetes mellitus ```

Question 26

Type 2 diabetes

Answer 26

Normal secretion but relative peripheral insulin resistance - defective insulin receptor mechanism- change in receptor number and/or affinity - excessive or inappropriate glucagon secretion

Question 27

synthesis of insulin

Answer 27

1. The single polypeptide preproinsulin is synthesised in the nucleus of β-cells. 2. A signal peptide on the preproinsulin directs the polypeptide chain to the rough endoplasmic reticulum. 3. Preproinsulin is cleaved to proinsulin. 4. The proinsulin is folded and the disulphide bridges are formed. 5. Proinsulin is transported to the golgi apparatus where it is cleaved to produce insulin and C-peptide, which are both packaged into a secretory granule that then waits for a signal to be released.

Question 28

how is insulin released

Answer 28

1. Food intake results in an increase in blood glucose concentration. 2. Glucose diffuses into the pancreatic β cell via GLUT2 transporters. 3. The increase in intracellular glucose causes an increase in glycolysis and ATP production. 4. The increase in ATP production increases the intracellular ATP:ADP ratio. 5. The increased ATP:ADP ratio causes the ATP-dependant K+ channels on the cell membrane to close. 6. The closure of the K+ channels causes the membrane to depolarise. 7. Voltage-gated Ca2+ channels on the cell membrane open, and there is a calcium influx into the cell. 8. The increase in intracellular calcium causes secretory granules to be released via exocytosis.