Endocrinology III: Diabetes Flashcards
What are the two types of functions the pancrease can carry out
Endocrine function- islets of langrrhan have cells to regulate blood glucose conc
Exocrine function- secrete proteases and lipases to digest food
What type of cells are in islets of langerhan
β-cells= secrete insulin
α-cells= secrete glucagon
δ-cells= secrete somatostatin
γ-cells= pancreatic polypeptide
What is the neurovasuculture supply of islets
Blood supply from afferent arterioles of pancreatic duodenal arteries that allow it to monitior blood glucose and rapidly spread secretion
Innervated by Vagus (PNS) and greater, middle splanchnic (SNS)
What is the process to synthesize insulin
long polypeptide chain pre-proinsulin is formed with a signal sequence at N-terminal, which takes it to vesicles.
The signal sequence is removed to form proinsulin. Futher cleavage results on removal of connecting peptide (C-peptide) to form C-peptide and insulin, which are both secreted out of β-cells
How is glucagon released
it is triggered by hypoglycaemia and L-arginine is a potent stimulator for glucgon release from α-cells, which then increases glycogenolysis in the liver
What is the function of somatostatin
inhibits the release of insulin, glucagon and pancreatic PP. ALso inhbitis gastric acid secretion, contraction of gall bladder and resuces intestinal otility and absorbiton, delayers increase in blood glucose until insulin and glucagon has been released and exhurted their effects
How do the hormones interact with each other
insulin inhibits glucagon release
glucagon promoted insulin and somatostatin release
Somattostatin inhibits insulin and glucagon release
How does glucose stimulate insulin release
Glucose enters cell via GLUT2 transporter and is converted by glucokinase into glucose-6-phosphate, this enters the glycolysis cycle to make lots of ATP, which causes the closure of K+channels causing membrane depolarisation opening Ca2+ channels leading to Ca2+ entry into cell, which cause exocytosis of insulin-containing vesicles
What do incretin hormones do
GLP-1, is secreted by L-cells in distal gut to stimulate insulin secretion and inhibits glucagon release
GIP secret by K cells in proximal gut to stimulate insulin secretion
How does glucagon cause insulin relase and why
Glucagon receptor are Gs, so when it binds it forms …. PKA which causes mobilitsation of insulin-containing vesicles to exocytose, as insulin is needed to allow glucose uptake into cells and prevent hyperglycaemia after glucagon done its ting
How do sulphonylurease (gliclazide) and glinides
bind to SUR1 receptors on ATP-K channels on β-cells, which close the K+ channels causing depolarisation and Ca2+ influx
How do β-cells stimulate each other to cause high secretion of insulin
6 connexins make a connexon of 1 β cell, which will bind to the connexon of another β cell to connecting each ones connexons create a channel, meaning that when one of the cells has been activted by glucose, the molecule can pass through the channels to another β-cell activating secretion
What is pathophysiology of Type 1 diabetes
mutation involving autoreactive CD4+ and 8+ cells recognise pancreatic antigens such as insulin and glutamic acid decarboxylase (GAD- makes GABA) causing killing of β-cells
What is pathophysiology of Type 2 diabetes
High levels of glucose in blood cause increase glycation of proteins to make AGEs, which are pro-inflam cytokines causing tissue damage and inflam, whoch causes increase fat deposition and protein deposistion in vessels causing atheosclerosis. AGE products cause damage/ thickening of capillary basement membrane
Fatty liver causes increase FFA in blood and chronic exposure on β-cells causes decreased sensitivity of glucose on the cells.
Glucose is converted to sorbitol in veins ,which is then converted to fructose via sorbitol dehydrogenase. Some tissue (PCT, Schwann cells, densa of eyes) dont contain this enzyme leading to increase sorbtiol levels in these cells, which is a powerful osmotic agent causing osmotic cell death
How does proteinuria occur
Due to AGE, ROS, sorbitol the basement brane is damaged allowing more protein such as albumin to escape into urine
