13 Endocrine Pancreas Flashcards
Where does the pancreas sit in the body?
How does the pancreas develop?
=Large gland
=Outgrowth of foregut (embryologically)
What are the 2 functions of the pancreas?
- Exocrine: Produce digestive enzymes secreted directly into duodenum- alkaline secretions via pancreatic duct to duodenum
- Endocrine: Hormone production- from islets of Langerhans
What % of the pancreas as a whole is exocrine and what % is endocrine?
Endocrine= 1%
Exocrine= 99%
What are the arrows in the following diagram showing?
Islets of langerhans
Describe the blood supply to the Islets of Langerhans.
Blood supply= in close proximity
Name the 7 polypeptide hormones secreted by the pancreas and the islet cells that release them:
Complete the missing gaps in the following table:
Name a tissue that is very sensitive to plasma glucose.
The brain
What levels should glucose be at?
Normal: 3.3-6 mmol/L
After a meal: 7-8 mmol/L
Renal threshold: 10 mmol/L
How would a patients urine be described if the renal threshold was exceeded?
Glycosuria
How are insulin and glucogon carried in the blood?
Water soluble hormones- carried dissolved in plasma
Short half-life: 5mins
How do insulin and glucagon carry out their function?
- Interact with cell surface receptors on target cells
- Receptor with hormone bone can be internalised- inactivation
Why is insulin ‘anti-gluconeogenic’?
(it is also anti-lipolytic and anti-ketogenic)
- At high dosage
- –> lowers incorporation of pyruvate into blood glucose
- –> stimulates pyruvates incorporation into liver glycogen
What is the polypeptide structure of insulin?
Big peptide with alpha helix structure
What’s the pathway of insulin from rER to exit the cell?
- Pre-proinsulin translation, signal cleavage, proinsulin folding
- Proinsulin transported to golgi
- Proinsulin cleaved to produce insulin and C-peptide
- Secretory granule formation
How are KATP channels regulated by metabolism?
- Metabolism high:
- KATP channels shut
- Insulin secretion
- Metabolism low:
- opens KATP channels
- NO insulin secreted
What does insulin do?
Increases glucose uptake into target cells and glycogen synthesis in:
- Liver
- stimulate glycogen formation and inhibit its breakdown
- inhibits breakdown of amino acids
- Muscles
- increases uptake of amino acids promoting protein synthesis
- Adipose tissue
- increases storage of tryglycerides
Describe the insulin receptor.
- On cell surfaces
- dimer
- 2 identical subunits span cell membrane
- alpha chain on exterior
- beta chain on interior
Through what channel is glucose taken up into target cells?
Glut 4 channel
What are the functions of glucagon?
- Raise blood glucose levels
- Glycogenolytic
- Gluconeogenic
- Mobilises energy release
- Lipolytic
- Ketogenic
What triggers glucagon to be released?
Low glucose levels in alpha cells
How is glucagon synthesised and secreted?
- Synthesised in rER in alpha cells
- Transported to Golgi
- Packaged in granules
- Margination- storage vesicles (granules) move to cell surface
- Exocytosis- fusion of vesicle membrane with plasma membrane- release contents
Why does glucagon have a simpler synthesis than insulin?
Larger precursor molecule
What effects does glucagon have in the body?
(primarily liver)
- Liver
- increases glycogenlysis- rate of glycogen breakdown
- stimulates pathway synthesis of glucose from amino acids (Gluconeolysis)
- Stimulate lipolysis-
- increase plasma fatty acid
NET EFFECT= rise in blood glucose levels
When might glucose be given clinically?
Diabetic:
- Experiencing hypoglycaemia
- Cannot take sugar orally
If the insulin levels are abnormal (too high or too low) what does it cause?
High- hypoglycaemia
Low- hyperglycaemia (diabetes mellitus)
If the glucagon levels are abnormal (too high or too low) what does it cause?
High: makes diabetes worse
Low: may contribute to hypoglycaemia
What is diabetes mellititus?
- Group of metabolic diseases
- Affects >2% of population (UK)
- Chronic hyperglycaemia
- Causing long-term clinical complications
- Associated w./ glycosuria
- Chronic hyperglycaemia
How do we diagnose diabetes?
Venous plasma glucose concentration
A patient may be diagnosed as diabetic if their blood glucose levels are outside of what range?
What causes Type 1 diabetes?
(Absolute immune deficiency)
- Autoimmune destruction of Pancreatic Beta-cells can be:
- ABSOLUTE: cells destroyed
- RELATIVE: secretory response of cells abnormally slow or small- defective beta cells/beta cell loss
What happens to the KATP channels in an insulin deficiency?
They become less ATP sensitive
What causes (at the cellular level) Type 2 diabetes?
Normal secretion but relative peripheral insulin resistance:
- Defective insulin receptor mechanism
- change in receptor number
- change in receptor affinity
- Defective post receptor events
- Excessive/inappropriate glucogon secretion
What are the main sites of glucose utilisation which would show decreased response to circulating insulin?
Adipose
Liver
Skeletal
Outline how a person develops insulin resistance in 3 steps:
- Beta cells compensate for inital hyperglycaemia by increasing insulin production- normal blood glucose maintained
- Beta cells unable to maintain insulin production- impaired glucose tolerance
- Beta cell dysfunction- causes relative insulin deficiency
Complete the table with either a + or -
Complete the table with either a +or -
