S7 L1 - The Endocrine Pancreas Flashcards
Anatomy of the pancreas
Development of the gut
Pancreas functions
Anatomy of the pancreas:
Head, body, tail
Gland looks like a fish, has a close relationship to the stomach
Development of the gut:
Forgut, mid gut, hind gut
The pancreas develops embryologically as an outgrowth of the foregut
- *Functions of the pancreas:**
- EXOCRINE (99%): Produces digestive enzymes secreted directly into duodenum (exocrine action) • Exocrine function forms the bulk of the gland
- ENDOCRINE (1%): Hormone production (endocrine action) • From Islets of Langerhans
- *Exocrine function**
- What does the histology of a pancreas showing both endocrine and exocrine sections look like?
- Endocrine functions and the major cell types in islets
- What does the histology of a pancreas showing both endocrine and exocrine sections look like?
Arrows are pointing to Islets of Langerhan cells
- Endocrine functions and the major cell types in islets
• Beta (β)-cells - Insulin
• Alpha (α)-cells - Glucagon
• Delta (δ)-cells - Somatostatin
• PP cells - PP
• Epsilon (ε) cells - Ghrelin
• G cells - Gastin
- *Hormones - Glucose regulation**
- Overall/brief role of insulin and glucagon
- What is the: signal, target tissue, affect on metabolism (which ‘groups’), actions, for insulin and glucagon
- What is the normal range for glucose (fasting)
- What is the normal range for glucose (after a meal)
- What is the renal threshold? Above this threshold, what happens?
- Which ‘conditions’/situations is the renal threshold different?
- Properties of insulin and glucagon - how is it carried in the blood? Half life?
- Overall/brief role of insulin and glucagon:
Regulation of metabolism of carbohydrates, proteins, and fats
• Insulin - lowers blood glucose levels
• Glucagon - raises blood glucose levels
- What is the: signal, target tissue, affect on metabolism (which ‘groups’), actions, for insulin and glucagon
pic
- What is the normal range for glucose (fasting)
4-7mmol/L
- What is the normal range for glucose (after a meal)
7-8mmol/L
- What is the renal threshold? Above this threshold, what happens?
10mmol/L
If above, get sugar in urine, this is called glycosuria
- Which ‘conditions’/situations is the renal threshold different?
– Pregnancy - lower renal threshold
– Elderly - higher renal threshold
- Properties of insulin and glucagon
– It is dissolved in plasma (no transport protein)
– Half life is 5 mins
Role of Insulin - How does it affect: Carbohydrate, lipid and protein metabolism
General:
- increases uptake into tissues
- Stimulates their synthesis
- Inhibits their breakdown
- *Carbohydrate metabolism:**
- Increases glucose transport across the cell membrane
- Stimulates glycogen synthesis
- Inhibits glycogen breakdown
- *Lipid metabolism:**
- Increases uptake of triaglycerides from the blood
- Stimulates fatty acid and tracylcerol synthesis
- Inhibits lipolysis in adipose tissue
- *Protein metabolism:**
- Increase transport of some amino acids into tissue
- Stimulates protein synthesis in muscle, adipose tissue, liver, and other tissues
- Inhibits proteind degradation in muscle
INSULIN IS ANABOLIC
Insulin Synthesis
PreproInsulin Structure
Cellular and Physiological effects of C-peptide
- Any influence on metabolism?
- New ideas
Insulin Synthesis:
1. Prepro-insulin translation, signal cleavage, proinsulin folding. Now it is proinsulin
2. Proinsulin is transported to Golgi
Proinsulin - insulin and C-peptide
3. Proinsulin is cleaved to produce insulin and C-peptide
4. Margination (movement of the vesicle to the cell surface)
5. Exocytosis (releasing the contents of the vesicle)
Pre-pro-insulin Structure:
51 amino acids
2 polypeptide chains with alpha helix structure
3 bits: A chain, B chain and C-peptide
The two chains are connected by 2 disulphide bridges
Cellular and Physiological effects of C-peptide:
No influence on glucose or lipid metabolism, so regarded as waste. However, now scientists believe it has a purpose e.g. improve nerve function…
- *Recap on - Potassium ions and membrane potentials (think back to action potentials)**
- Describe an action potential
- Na+ ions enter - depolarise the cell
- K+ ions leave - hyperpolarise the cell
Insulin secretion
- Which cells is insulin secreted from?
- How is insulin secreted?
- How does insulin stop being secreted from cells?
Which cells is insulin secreted from?
Beta cells in Islets of Langerhans
How is insulin secreted?
- Glucose concentration in the blood is high
- Glucose enters the beta cells through GLUT2 channels
- Glycolysis of glucose, releases ATP
- ATP concentration increases - ATP is high : ADP is low
- ATP inhibits KATP channels
- This reduces K+ efflux
- RMP depolarises
- Ca2+ voltage gated channels on the cell membrane open
- Influx of Ca2+
- Secretory channels containing insulin fuse with the membrane, releasing the insulin (exocytosis)
How does insulin stop being secreted from cells?
- Glucose concentration is the blood is low
- Less glucose uptake into beta cells
- Less glycolysis
- Low ATP concentration
- KATP channels open
- K+ efflux
- Hyperpolarisation of the cell
- Ca2+ voltage gated channels shut
- No Ca2+ influx
- No insulin released
What does Insulin do when it is released into the blood stream?
- *Insulin receptor**
- Type
- Describe structure
- What happens when insulin binds to this receptor?
Increases glucose uptake into target cells and glycogen synthesis (insertion of Glut 4 channel )
Remember flashcard 4 -
• in the liver it increases glycogen synthesis by stimulating glycogen formation and by inhibiting breakdown
• in muscles it increase uptake of AA promoting protein synthesis
• in liver inhibits breakdown of AA
• in adipose tissue increases the storage of triglycerides • inhibits breakdown of fatty acids
Insulin receptor:
Type and structure:
• Insulin binds to the insulin receptor on cell surfaces
• receptor is a dimer
• two identical subunits spanning the cell membrane.
• two subunits are made of one α- chain and one β-chain, connected together by a single di-sulfide bond.
• α-chain on exterior of the cell membrane,
• β-chain spans the cell membrane in a single segment
- What happens when insulin binds to this receptor?
When insulin binds to the insulin receptor, a cascade of signalling mechanisms occurs, includes opening of GLUT4 allowing glucose to enters cells and enter pathways
- *Glucagon**
- Receptor type
- Role
- Synthesis
- Secreted by which cells and which mechanism?
Receptor type:
GPCR and G-alphas
Role:
Opposes insulin -
- Glycogenolytic
- Gluconeogeic
- Lipolytic
- Ketogenic
Synthesis and secretion:
- Synthesis in RER
- Transported to Golgi body, package in granules
- Margination - movement of storage vesicles to cell surface
- Exocytosis - fusion of vesicle membrane with plasma membrane with the release of the vesicle content
Secreted by which cells and which mechanism?
Secreted by alpha-cells, secreted due to low glucose levels in alpha-cells
Mechanism of regulation of secretion remains poorly defined, but KATP channels of the same type found in beta-cells are likely involved
- *Glucagon**
- Structure
- Clinical use
Structure:
• 29 amino acids in 1 polypeptide chain
• No disulphide bridges: = flexible structure
• Simpler synthesis than insulin
• larger precursor molecule (pre- proglucagon)
• undergoes post-translational processing to produce the biologically active molecule.
Clinical use:
Glucagon in emergency medicine is used when a person with diabetes is experiencing hypoglycaemia and cannot take sugar orally
Recap -
Summary of Insulin and Glucagon role in metabolism
- Carbohydrate
- Lipids
- Proteins
What happens if give too much or too little of insulin
What happens if give too much or too little of glucagon
Summary of Insulin and Glucagon role in metabolism
- Carbohydrate
- Lipids
- Proteins
(see pic)
What happens if give too much or too little of insulin:
• High – hypoglycaemia. • Low – hyperglycaemia -diabetes mellitus
What happens if give too much or too little of glucagon:
• High – makes diabetes worse • Low – may contribute to hypoglycaemia
