The Endocrine Pancreas Flashcards
What are the exocrine and endocrine functions of the pancreas?
Exocrine - Pancreatic acini secrete enzymes active in protein, fat and carb digestion.
Endocrine - pancreatic islets produce hormones.
What are the various types of cell types of islets of langerhans?
- Alpha cells - produce glucagon.
- Beta cells - produce insulin and amylin (majority of islet cells),
- Delta cells - produce somatostatin,
- Epsilon cells - produce ghrelin,
- PP cells - pancreatic polypeptide
Describe the synthesis of insulin
- Transcription of insulin gene,
- mRNA encoding preproinsulin,
- Translation of preproinsulin (the protein is synthesis directly into the endoplasmic reticulum),
- Converting enzymes and cleavage of connecting peptide (C-peptide), formation of disulphide bonds and crystallisation
- Results in mature insulin in secretory granule
Explain the microvasculature and innervation of the endocrine pancrease
- Each islet is encapsulated and innervated with a capillary bed. This facilitates rapid delivery of pancreatic hormones into the circulation.
- Insulin secretion is stimulated by activation of parasympathetic nerves and inhibited by activation of sympathetic nerves.
What is the main factor involved in regulating insulin secretion?
Blood glucose levels. This stimulated beta cells to produce insulin.
What are other factors that potentiate the release of insulin
- Amino acids and fatty acids stimulate the beta cells.
- Gut hormones which are activates by the digestion of food also stimulates beta cells. This only occurs when there is oral digestion of food. IV glucose produces a reduced incretin effect.
- Parasympathtic release of Ach on muscarinic receptors activate beta cells.
- Alpha cells release glucagon which activates beta cells
What are some factors that inhibit the release of insulin
- Sympathetic nerves release noradrenaline which binds to alpha-2 receptors inhibiting beta cells.
- Delta cells release somatostatin which inhibits beta cells but also acts indirectly by inhibiting alpha cells, reducing the release of glucagon.
Describe the cellular mechanism involved in the release of insulin from beta cells
- Glucose enters cells via GLUT2 receptors.
- Glucose then undergoes glycolysis which results in formation of pyruvate which can then be fed into the citric acid cycle resulting in formation of ATP.
- ATP inhibits potassium channels causing the cell to depolarise which results in opening of voltage gated calcium channels.
- Calcium enters the cell and binds to receptors on the endoplasmic reticulum, causing the release of more calcium. Elevated calcium leads to exocytosis of secretory granules and release of insulin into the blood stream release
Explain how other modulators of insulin secretion act on a cellular level
- Amino acids and fatty acids can pass into the cell and be fed into the citric acid cycle resulting in formation of more ATP.
- Gut hormones act increasing calcium levels or increasing cAMP.
- Somatostatin supresses adenyl cyclase which reduced cAMP which leads to less phosphorylation of proteins involved in exocytosis.
What are the physiological actions of insulin
- Increases glucose transport into muscle and adipose cells.
- Increased glycogenesis in the liver and muscle. (liver expresses GLUT2 receptors, these are not recruited by glucose and so is a major site of glycogen storage)
- This results in a decreased blood glucose level.
- Also causes increased protein synthesis for growth and maintenance,
- Increased lipogenesis in the liver and adipose tissue
What are factors that regulate glucagon release?
- Amino acids and low glucose in the blood activated alpha cells.
- Gut hormones can either activate or inhibit alpha cells.
- Parasympathetic and sympathetic nerves can activate alpha cells.
- D cells secrete somatostatin which inhibits alpha cells.
- B cells release insulin which inhibits alpha cells
What are the physiological actions of glucagon?
- Increased glycogenolysis in the liver causing increase in blood glucose,
- Causes an increase in cortisol which increases gluconeogenesis in the liver and kidney which leads to an increase in blood glucose.
- Decrease in insulin caused decreased lipogenesis in the liver and increased lipolysis in adipose tissue. This causes an increase in fatty acids and glycerol (glycerol causes increase in gluconeogenesis)