8.1 - endcrinology Of the Pancreas

Question 1

What’s the function of the pancreas??

Answer 1

Produce digestive enzymes secreted directly into the duodenum (exocrine action) by acinar and duct tissue

Hormone production (endocrine action) from islets of langerhans

Question 2

What 5 cells produce which 5 hormones in the pancreas?

Answer 2

Beta cells = insulin
Alpha cells  = glucagon.  
PP cells = PP (pancreatic polypeptide)
E cells = ghrelin
G cells = gastric

Question 3

Is glucagon catabolic or anabolic?

Answer 3

Catabolic - breaks down stores of carbs and lipids

Question 4

What is the importance of plasma glucose?

Answer 4

Brain uses glucose at fastest rate in body, and is sensitive to falls or rises in glucose = needs to be controlled.

Renal threshold = the point which glucose appears in the urine 10 mmol/L

Question 5

What are the shared properties of Insulin and glucagon?

Answer 5

Water soluble hormones

• carried dissolved in plasma
• short 1/2 life
• interact with cell surface receptors on target cells
• receptor with hormone bound can be internalised = inactivation

Question 6

What is the role of insulin?

Answer 6

Is anti-gluconeoenic

Anabolic

Question 7

How do B cells synthesise insulin?

Answer 7

1) pre pro insulin is synthesised, cleaved in the rER and folded to form proinsulin
2) pro insulin is transported to Golgi
3) proinsulin is cleaved t produced insulin and C peptide
4) insulin granules sit on the inside of the membrane until change in membrane potential allows Ca2+ influx so they go out

Question 8

How does insulin secretion affect Katp channels?

Answer 8

No insulin released

• metabolism low
• Katp channels open
• no insulin secreted
• membrane hyperpolarised
• Ca channels closed

Insulin released

• metabolism high
• Katp channels shut
• insulin secretion
• membrane depolarised
• Ca channels open

Question 9

What are the effects of insulin?

Answer 9

increases glucose uptake into target cells and glycogen synthesis (inserts Glut 4 channel)

• in liver, increases glycogen synthesis by stimulating glycogen formation by inhibiting breakdown
• in muscles, increases AA uptake promoting protein synthesis
• in liver inhibits breakdown of AA
• in adipose tissue increases the storage of triglycerides

Question 10

How does glucose enter The cell?

Answer 10

Insulin binds to insulin receptor and this causes a change in the shape of the GLUT4 transporter = glucose can enter the cell

Question 11

What does glucagon do?

Answer 11

• secreted by alpha cells when glucose levels low
• synthesised in rough ER and packaged in granules in Golgi
• effect mainly liver

Question 12

What’s the structure of insulin?

Answer 12

Two unbranded chains connected by 2 disulphides brides = ensures stability.
2 polypeptide chains and 2 disulphide bridges = Rigid

Question 13

What’s the structure of glucagon?

Answer 13

1 long polypeptide chains

Flexible, no disulphides bridges

Question 14

What are the effects of glucagon?

Answer 14

• Increases rate of glycogen breakdown (glycogenolysis)
• stimulates pathway for synthesis of glucose from AA (gluconeogenesis)
• net effect = rise in blood glucose
• stimulates lipolysis to increase plasma fatty acid

Clinically used for a diabetic experiencing hypoglycaemia who cant take sugar orally.

Question 15

What’s diabetes mellitus?

Answer 15

Group of metabolic diseases
Characterised by
- chronic hyperglycaemia
- leading to long term clinical complications

Associated with elevated glucose levels in urge

Question 16

How is diabetes mellitus diagnosed?

Answer 16

Based on venous plasma concentration

Question 17

How is type 1 diabetes mellitus caused?

Answer 17

Type 1 = absolute insulin deficiency

Absolute - autoimmune destruction of pancreatic B cells
Relative - secretory response of B cells is abnormally slow or small (failure to secrete adequate amounts of insulin)

Question 18

How do Katp channels change in insulin deficiency?

Answer 18

Less ATP sensitive so will remain open when glucose is entering the cell = membrane stays hyper polarised
No insulin released

Question 19

What is type 2 diabetes mellitus caused by?

Answer 19

Type 2 = normal secretion but peripheral insulin resistance

• defective insulin receptor mechanisms = change in number/affinity
• defective post receptor events e.g tissues become insensitive
• excess/ inappropriate glucagon secretion

Combo of genetic and environmental factors e.g obesity and sedentary lifestyle.

Question 20

How does insulin resistance in the young occur?

Answer 20

Before 12 = onset of hyperglycaemia and development of overt type 2

Initially = B cells compensate by increasing insulin production so normal blood glucose is maintained

Eventually = B cells unable to maintain increased insulin production - impaired glucose tolerance

Finally = B cell dysfunction leads to relative insulin deficiency - overt type 2 diabetes