Week 18 Physiology

Cell types in Islets of Langerhans

• Insulin – B – 68%
• Glucagon – a – 20%
• Somatostatin  – d – 10% (inhibit other 2)
• Pancreatic polypeptide – f cells
• 1-2% of pancreas

 

Insulin

• Structure.
  • 2 chains of amino acids joined by a disulfide bridge
• Synthesis / secretion.
  • Initially synthesised as preproinsulin then cleaved to insulin by time of release.
  • Made in RER –> packaged in membrane bound granules in golgi appatatus and transported out via exocytosis and then enters blood vessel via fenestrations
• Effects.
  

  Ganong’s Review of Medical Physiology, 24th Edition

  • Liver
    • Decrease ketogenesis
  • Muscle
    • Increase ketone uptake
  • Adipose
    • Increase fatty acid synthesis
    • Increase TG deposition
    • Inhibit hormone sensitive lipase.
• Mechanism of action
  • T 1/2 5mins
  • Insulin binds to insulin receptors –>tyrosine kinase activity of receptor in tracellular side–>  autophosphorylation of beta sub units of insulin receptor–> activation of phosphatidyl ionositol 3-kinase –> anabolic effect and increases glucose transporters etc
• Factors affecting insulin secretion.

• 

  Ganong’s Review of Medical Physiology, 24th Edition

 

Glucagon:

• Actions
  • –> increase plasma glucose
  • Increase glycogenolysis
  • Increase gluconeogenesis
  • Increase protein break down
  • Increase lipolysis
  • Increase ketogenesis
  • Acts via G protein receptor –> adenyl cyclese–> increase cAMP –> increase activity of protein kinase A
  • Can also activate phosphokinase C –> increase Ca2+
  • In large doses its positively ionotropic
  • Stimulates secretion of growth hormone, insulin and somatostatin

• Factors affecting secretion.

• 

  Ganong’s Review of Medical Physiology, 24th Edition

 

Somatostatin:

• Actions.
  • Paracrine way to inhibit secretion of insulin, glucagon and pancreatic polypeptide

• Factors affecting secretion.
  • Increased by glucose, amino acids(esp arginine and leucine), and CCK.

 

Pancreatic polypeptide.

• Secreted – cholinergic stimuli, protein containing meal, fasting, exercise, hypoglycaemia
• Inhibited – somatostatin, glucose
• Action – slows absorption of food

 

Basic overview of “Endocrine regulation of carbohydrate metabolism”.

Exercise promotes insulin independent increase of GLUT4 channels in muscle –> increased insulin sensitivity and can prompt hypoglycaemia in diabetics

• Catecholamine
  • B agonists  –> increase intracellular cAMP
  • A agonists –> increase intracellular Ca2+
  • In liver this causes increased glucose release –> hyperglycaemia initially
  • Later glycogen synthesis
  • FFA release

• Thyroid hormones
  • Increase Glucose absorption from GIT, increase insulin breakdown and increase glycogenolysis in liver
  • Diabetogenic

• Glucocorticoids
  • The glucocorticoids are necessary for glucagon to exert its gluconeogenic action during fasting. They are gluconeogenic themselves, but their role is mainly permissive.
  • In deficiency, fasting can precipitate hypoglycaemia.

• Growth hormone
  • Worsens diabetes
  • Increases FFA, decreases glucose uptake into cells, increase hepatic glucose output–> hyperglycaemia–> stimulate insulin release

 

Pancreas

• Retroperitoneal organ
• Secretes 2-2.5L per day
• Proenzymes
  • Tryprsinogen
  • Chymotrypsinogen
  • Procarboxypeptidase
  • Proelastase
  • Kallikreinogen
  • Phospholipase A
  • Conversion of proenzymes requires conversion of trypsinogen to tripsin by duodenal enteropeptidase.
• Enzymes released in active form
  • Lipase
  • amylase

 

Viva questions:

1. Tell me about the endocrine functions of the pancreas.
2. Tell me about the exocrine functions of the pancreas.
3. Tell me about insulin.
4. Tell me about the actions of insulin.
5. What factors affect insulin secretion ?
6. How does insulin work ?
7. Tell me about Glucagon.
8. What factors affect glucagon secretion ?
9. Tell me about control of blood glucose level