Session 7- The Endocrine Pancreas Flashcards
What is acute chest syndrome
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
Function of pancreas
Produce digestive enzymes secreted directly into duodenum- exocrine function which forms the bulk of the gland
Hormone production from islets of langerhans
Staining of pancreas
Dark stain- exocrine tissue
Light pale blobs- islets of langerhands
What is plasma glucose normally
3.3-6 mmol/L
What is plasma glucose after a meal
7-8 mmol/L
Renal threshold of plasma glucose
10 mmol/L
When is glycosuria normal
Pregnancy
Elderly renal threshold increases
What does insulin promote
Carbohydrate metabolism
Lipid metabolism
Protein metabolism
Insulin is anabolic, antigluconeogenic, anti-lipolitic, anti-ketotonic
Insulin synthesis
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
What does insulin consist of
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
KATP Channels regulated by metabolism
Glucose closes kATP channels in pancreatic beta cells
Metabolic inhibition reopens kATP channels
How does metabolism affect insulin secretion
Metabolism is low, KATP channels open, no insulin secreted
Metabolism high, KATP channels shut, insulin secreted
What channels do glucose enter cells through and when
GLUT2 channels at 7mM
How does ATP affect kATP channels
ATP inhibits the channel activity and reduced K+ efflux
This tiggers exocytosis of insulin
What dos insulin do
Increases glucose uptake into target cells and glycogen synthesis via GLUT4 channel
What does insulin do in the liver
It increases glycogen synthesis by stimulating glycogen formation and by inhibiting breakdown
What does insulin do in muscles
Increases uptake of AA promoting protein synthesis
Inhibits breakdown of AA
What does insulin do in adipose tissue
Increases the storage of triglycerides
Structure of insulin receptor
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
Glucagon
- acts to raise blood glucose levels
- It is glycogenolytic,
- gluconeogeneic
- lipolytic
- ketogenic
Margination
Movement of storage vesicles to cell surface
Exoytosis
Fusion of vesicles membrane with plasma membrane with he release of the vesicles contents
Effects of glucagon on liver
Increase rate of glycogen breakdown- glycogenolysis
Effects of glucagon
- Gluconeogenic
- Stimulates lipolysis to increase plasma fatty acid
- glycogenolysis
What are te potassium ATP channels like in insulin deficiency
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
Type 2 diabetes
Normal secretion but relative peripheral insulin resistance
- defective insulin receptor mechanism- change in receptor number and/or affinity
- excessive or inappropriate glucagon secretion
synthesis of insulin
- The single polypeptide preproinsulin is synthesised in the nucleus of β-cells.
- A signal peptide on the preproinsulin directs the polypeptide chain to the rough endoplasmic reticulum.
- Preproinsulin is cleaved to proinsulin.
- The proinsulin is folded and the disulphide bridges are formed.
- 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.
how is insulin released
- Food intake results in an increase in blood glucose concentration.
- Glucose diffuses into the pancreatic β cell via GLUT2 transporters.
- The increase in intracellular glucose causes an increase in glycolysis and ATP production.
- The increase in ATP production increases the intracellular ATP:ADP ratio.
- The increased ATP:ADP ratio causes the ATP-dependant K+ channels on the cell membrane to close.
- The closure of the K+ channels causes the membrane to depolarise.
- Voltage-gated Ca2+ channels on the cell membrane open, and there is a calcium influx into the cell.
- The increase in intracellular calcium causes secretory granules to be released via exocytosis.