MEH 13 - The Endocrine Pancreas Flashcards
Where is the pancreas found?
What is the blood supply for the pancreas?
- In close relationship to the stomach, head nestles into the curvature of the duodenum. Consists of head, body and tail.
- The pancreas develops as an outgrowth of the foregut so is supplied by the coeliac trunk.
What are the 2 (exocrine + endocrine) functions of the pancreas?
1) Produces digestive enzymes secreted directly into duodenum (exocrine) - forms bulk of the gland (~99%)
2) Hormone production (endocrine) from islets of langerhans (~1% of the pancreatic mass)
What are the important polypeptide hormones secreted by the pancreas + which cells do they come from?
B-cells = Insulin A-cells = Glucagon D-cells = Somatostatin PP cells = Pancreas Polypeptide G-cells = Gastrin Epsilon cells = Ghrelin
What is the role of insulin + glucagon?
What signal stimulates their release?
What are their target tissues?
What do they affect metabolism of?
- A meal/feeding increases plasma glucose stimulating insulin release. They act on liver, adipose + skeletal muscle to make carbohydrates, lipids + proteins in an anabolic fashion.
- A decrease in plasma glucose/fasting stimulates glucagon release. Glucagon acts on liver + adipose tissue to cause breakdown of carbohydrates and lipids in a catabolic fashion.
NB: normal plasma glucose = 3.3-6mmol/L, increase in 7-8 after a meal.
What are the properties of the water soluble hormones Insulin + Glucagon?
- Carried in plasma, no special transport proteins.
- Short 1/2 life (5 mins)
- Bind to cell surface receptors which can be internalised
What are the 3 primary actions of insulin?
1) Carbohydrate metabolism = increases glucose transport into cell, increases glycolysis (glucose breakdown) + stimulates glycogen synthesis
2) Lipid metabolism = decreases lipolysis, stimulates FA + TAG synthesis.
3) Protein metabolism = increases transport of AA’s into tissues + increases protein synthesis.
- Anabolic, anti-gluconeogenic, anti-lipolytic.
Describe the process of insulin synthesis
1) Pre-proinsulin cleaved to form pro-insulin in the RER, moved to golgi apparatus
2) Pro-insulin cleaved in golgi apparatus to produce insulin AND c-peptide.
3) Vesicles containing insulin + c-peptide marginated to sit under cell surface as a secretory granule, released via exocytosis when signal arrives.
What is the molecular structure of insulin?
- Large peptide with alpha helix structure
- 2 x unbranched peptide chains connected by 2 disulphide bridges.
- 51 AA’s, 2 polypeptide chains.
How are ATP sensitive K+ channels involved in regulation of insulin secretion?
- When glucose/metabolism is low, so is ATP production. Katp channels stay open, causing hyperpolarisation (efflux of K+), so no insulin is secreted.
- When glucose/metabolism is high, so is ATP production. A high ATP/ADP ratio causes Katp to shut, so cell becomes depolarised. DP causes opening of Ca2+ channels which triggers exocytosis of insulin containing vesicles (insulin secretion).
What are the effects of insulin?
- Increased glucose uptake into target cells via insertion of GLUT4 channel into membrane
- Increases glycogen synthesis in the liver
- Increased uptake of AA’s in muscle to promote PS
- Inhibits breakdown of AA’s in liver
- Increases storage of TG’s in adipose tissue/inhibits FA breakdown
Describe the process of glucagon synthesis + release
- Synthesised in RER + transported to golgi
- Packaged in granules, moved to cell surface (margination)
- Released via exocytosis upon appropriate stimulus
Describe the structure + effects of glucagon
- 29 AA’s in 1 polypeptide chain, no disulphide bridges. Synthesis similar to insulin (pre-proglucagon precursor)
- Glycogenolysis in the liver
- Stimulate gluconeogenesis
- Stimulates lipolysis to increase plasma FA’s
How is diabetes diagnosed?
- On plasma glucose conc
- Fasting conc >7mM/L
- Random conc >11mM/L
- HbA1c (glycated Hb) >48mmol/L
