13- The Endocrine Pancreas

Question 1

• where in the abdomen is the pancreas located?
• what are the 3 parts of the gut & what is their blood supply?in which part is the pancreas?
• what are the 2 main functions of the pancreas?

Answer 1

• located behind the stomach, tucked next to the duodenum (si), w aorta and portal vein behind it
• foregut (coeliac trunk), midgut (superior mesenteric artery, SMA), hindgut (inferior mesenteric artery, IMA), pancreas is in foregut
• produces digestive enzymes secreted directly into duodenum and produces hormones from islets of langerhans.

Question 2

• give 5 examples of important polypeptide hormones secreted by the pancreas & the cell that secretes them.
• give the functions of insulin & glucagon, what tissues they target and their relative actions (cat/anabolic)
• what organ uses glucose at the fastest rate?what’s the normal gluc concentration in blood?
• what’s the normal renal threshold? In what cases may it be different?

Answer 2

• insulin=beta, glucagon=alpha, somatostatin=delta, ghrelin=epsilon, Gastrin=g cells
• insulin lowers blood glucose, glucagon raises blood glucose, insulin targets liver, adipose and skeletal muscle (stores gluc), anabolic, glucagon targets liver and adipose, catabolic.
• brain, normal=3.3 to 6 mmol/L
• renal threshold=10mmol/L above this will have glycosuria, in elderly it’s higher, in pregnant women it’s lower so more likely to see glucose in urine tho it’s not always diabetes

Question 3

• give properties of insulin and glucagon.
• give the actions of insulin.
• outline the process of insulin synthesis.
• describe the structure of insulin
• what is the significance of C peptide and what can it tell us?

Answer 3

• water soluble hormones, carried dissolved in plasma not via transport proteins, interact w cell surface receptors
• FAVOURS STORAGE, stimulates glycogenesis, decreases lipolysis in adipose, increases protein synthesis, insulin is anabolic, anti gluconeogenic anti lipolitic, anti ketotonic
• pre pro insulin is translated, signal cleavage to form pro insulin then folding, proinsulin is transported to the Golgi, pro insulin is cleaved to form insulin and C peptide, then margination (movement of vesicles to cell surface)
• a big peptide w an alpha helix structure, has x2 unbranched peptide chains that are connected by 2 disulphide bridges ensuring stability
• when insulin is released, c peptide is also released at the same time. Therefore in an invective insulin poisoning there would be an increase in insulin but no c peptide increase

Question 4

• what role do K+ ATP channels have in insulin secretion?
• explain what happens in terms of glucose transporters when the glucose levels exceed 7mmol/L.
• give some metabolic effects of insulin.

Answer 4

• when glucose metabolism is low, K atp channels are open and no insulin is secreted, when gluc metabolism increases the K atp channels close and insulin is released.
• glucose enters cells via glucose transporters (GLUT2), glucose then is phosphorylated to G6P via glucokinase and enters the Krebs cycle, then oxidative phosphorylation to make ATP which then inhibits the K atp channels reducing the K+ efflux, mp is depolarised, Ca2+ channels increase their conductance leading to exocytosis of insulin in the vesicles
• increases glucose uptake into target cells, glycogen synthesis, inhibits breakdown of FAs

Question 5

• give some of glucagon’s functions
• where is glucagon synthesised and how is it secreted?
• give the structure of glucagon
• what is a useful clinical use of glucagon?
• why does glucagon stimulate protein synthesis instead of protein breakdown?

Answer 5

• acts to raise glucose levels, glycogenolytic, lipolytic, ketogenic, gluconeogenesis, mobilises energy release.
• synthesised in RER, transported to Golgi, effect is mainly in liver, secreted by alpha cells due to low glucose levels.
• 29 aa’s in 1 polypeptide chain, no disulphides bridges meaning it’s more flexible, simpler synthesis than insulin.
• in an emergency hypoglycaemia when an patient is not able to take glucose orally
• glucagon enhances aa catabolism, when proteins are administered alone there’s usually a large increase in glucagon and small increase in insulin.