The Endocrine Pancreas and Diabetes Mellitus Flashcards
The pancreas has a head, neck, body and tail and lies in close proximity to 3 major blood vessels. What are these and why is it significant?
The inferior vena cava, the portal vein and the superior mesenteric artery, which can be damaged if autolysis occurs (the pancreas is full of enzymes of digestion).
The pancreas is a large gland which develops embryologically from the foregut, what are its 2 functions?
Produces digestive enzymes secreted directly into the duodenum (exocrine function forms bulk), alkaline secretions through pancreatic duct.
Hormone production - endocrine action from Islets of Langerhans (1% of tissue which stain as pale blobs, ~0.3mm diameter, with insulin secreting beta cells in the middle, making up a larger proportion that alpha cells secreting glucagon on the outside).
The Islets of Langerhans produce 7 hormones, what are they, besides insulin and glucagon?
Somatostatin (delta cells), pancreatic polypeptide (PP cells), ghrelin (e cells) and gastrin (g cells), as well as vasoactive intestinal peptide.
Describe how 2 of the polypeptide hormones secreted by the pancreas have an effect on appetite.
Insulin works at the primary inhibitory neuron with a positive effect and ghrelin works at the primary stimulatory neuron with a positive effect.
Insulin lowers blood glucose and glucagon increases it; they generally oppose each other. How are they different in the signals that stimulate them, their target tissues, the types of metabolism they affect and the gist of their actions?
Insulin / glucagon:
Feeding / fasting,
Lipids, carbohydrates and proteins / lipids and carbohydrates,
Liver, adipose and skeletal muscle / liver and adipose,
Anabolic / catabolic.
Insulin canon work together to keep the plasma glucose levels fairly constant, why is this important?
The brain uses glucose at the fastest rate in the body (can used ketone bodies if trained when starving). It relies on the blood levels and is sensitive to falls or rises, which can be dangerous because glucose is an active osmole and so can cause cell shrinkage/swelling.
What are the parameters of blood glucose normally and after a meal? What about the renal threshold - how does this change with pregnancy and old age?
Normally 3.3-6mmol/L, and after a meal 7-8mmol/L. The renal threshold is 10mmol/L (after that you get glucosuria), which rises in old age and drops in pregnancy.
Properties of insulin and glucagon:
________ soluble hormones, carried ___________ in the plasma, with a short half life of only ___ minutes. They interact with cell __________ receptors and become inactivated, when bound to the receptor, they are _____________.
Water Dissolved 5 Surface Internalised
Insulin is anti-__________, anti-___________ and anti-___________. It is the hormone of energy __________ and anabolic.
Anti-gluconeogenic
Anti-ketotonic
Anti-lipolytic
Storage
Describe the structure of the hormone insulin.
The polypeptide hormone has an alpha helix structure and is made up of 2 unbranched peptide chains connected by 2 disulphide bridges to ensure stability (and rigidity). It contains 51 amino acids.
Describe the synthesis pathway of insulin in a pancreatic beta cell.
Preproinsulin (RER) -> proinsulin (Golgi), then mature insulin and C-peptide waiting in a vesicles. Margination then exocytosis - the daily secretion of insulin is only 15% of the total pancreatic stores.
Define margination and exocytosis in the context of insulin production and release.
Margination - movement of storage vesicles to the cell surface.
Exocytosis - fusion of vesicles membrane with plasma membrane and the release of the vesicle contents.
ATP sensitive potassium channels in pancreatic beta cells are regulated metabolism, how?
K-ATP channels without stimulation are open, leading to potassium efflux and hyperpolarisation of the cell membrane. However, when ATP is present, the channel is inhibited/blocked, exulting in depolarisation of the cell membrane and opening of the VOCC/L-type and calcium influx. This causes fusion of the vesicles with the cell membrane and insulin release.
Describe the insulin receptor.
It sits on the cell membrane and is a diner, with 2 identical subunits joined by a single disulphide bond (1 extracellular alpha and 1 beta, which spans the membrane).
What happens when insulin has bound to its receptor on the target tissue?
It binds to insulin and the efflux leads to the insertion of GLUT4 on the cell membrane (opening the door for glucose). It also stimulates the conversion of glucose, pyruvate and fatty acids (metabolic pathways for storage).
What are the metabolic effects of insulin (think of the different types of target tissue)?
Increase glucose uptake into target cells (insertion of GLUT4 channels) and glycogen synthesis. Stimulating glycogen formation and inhibiting its breakdown in the liver, increased uptake of amino acids, promoting protein synthesis and inhibiting amino acid breakdown in the liver. Also, inhibiting the breakdown of fatty acids and increase the storage of triglycerides in adipose tissue.
Glucagon is the hormone that opposes insulin, in what way?
It raises blood glucose levels, is glycogenolytic, gluconeogenic, lipolytic and ketogenic. It mobiles energy release (from stores).
Where, how and why is glucagon released?
Glucagon is secreted by pancreatic alpha cells due to low glucose. It travels from the RER to Golgi, is packaged in granules and its main effect is in the liver. Margination then exocytosis.
Glucagon is stimulated by adrenaline and noradrenaline (whereas insulin is stimulated by GI hormones).
