pancreas anatomy and physiology Flashcards
discuss the pancrease as an exocrine organq
- secretes digestive enzymes in response to gastrointestinal hormones
- secretes bicarbonate to neutralize acid produced in the stomach (in response to secretin)
- digestive enzymes: trypsin, lipase, amylase, phospholipase, ribonuclease and deoxyribonuclease
where are the endocrine cells of the pancrease located
in islets (islets of langerhans)
name the 3 different types of islet cells and what they produce
- beta = insulin (60-70%)
- alpha = glucagon (20-25%)
- delta = somatostatin (10%)
what other substances are released by the islet cells
- pacreatic polypeptide
- ghrelin
- vasoactive intestinal peptide
- secretin
- motilin
- substance P
what is somatostatin
where is it produced and what is the function
- produced by the hypothalamus, stomach, intestine and pancrease (delta cells)
- has paracrine function
- secreted by delta islet cells
- supresses insulin and glucagon secretion by local beta and alpha cells
what is insulin
- peptide hormone
- secreted by the beta cells of the islets of langerhans
- first synthesised as a preprohormone
- then converted to a prohormone called proinsulin
- stored as an intracytoplasmic pool of proinsulin waiting for secretion
describe the structure of insulin
- secretion involves removal of C-peptide from proinsulin
- insulin molecule consists of two polypeptide chains
describe the synthesis and secretion of insulin
synthesis:
1. preproinsulin
2. proinsulin
3. C-peptide cleaved from proinsulin = insulin (alpha and beta chains only)
discuss insulin kinetics and secretion
- insulin secreted by pancreatic cells
- only has a plasma half life of 5-8 minutes
- enters veins then into the portal system to act upon the liver first
- the insulin enters the general circulation
what are the 3 mechanisms for regulating insulin secretion
- increased nutrients (glucose and amino acids) recognized by islet cells, which secrete insulin to store excess
- gastrointestinal hormones (incretins) such as gastric inhibitory peptide and glucagon peptide prompts pancreatic cells to produce insulin
- ANS (PSNS stimulates insulin, SNS inhibits)
the release of insulin from beta cells occurs through the process of:
calcium mediated exocytosis
the action of insulin is to:
move excess nutrients into storage
describe how GLP-1 works
- released by small intestinal cells
- increase in secretion of GIP and GLP-1 when food reaches intesting
- causes insulin release from pancrease BEFORE nutrient absorption occurs
describe how the parasympathetic nervous system regulates insulin secretion
- increase in parasympathetic activity stimulates insulin secretion
- via the vagus nerve
- vagus nerve increases gastrointestinal motility and digestion
- higher insulin secretion after feeding
- SNS activity decreses insulin secretion
describe how the sympathetic nervous system regulates insulin secretion
- direct innervation
- indirect responses via adrenaline
- stress response = hyperglycemia
- insulin secretion is inhibited (as well as insulin action)
what are the key players in the release of insulin
- glucose transportes (GLUT 2: the islet glucose sensor)
- calcium
- potassium
- glucose
describe the sequence of events within the beta cells resulting in the release of insulin
- GLUT 2 transporters allow glucose to enter cell
- phosphorylation of glucose by glucokinase traps glucose in the cell
- increase in ATP production
- inhibits ATP-sensitive potassium channels
- increased intracellular potassium concentration leads to depolarization
- volatage gated calcium channels activated
- influx of calcium triggers exocytosis of insulin
explain the connection between insulin and insulin transporters
- insulin water soluble peptide hormone
- therefore requires receptor proteins to cross cell membrane
- density of receptors is determinant of insulin sensitivity
- activates the tyrosine kinase signal transduction pathway
what is mechanism of GLUT4
- insulin stimulates translocation of glucose transporter 4 proteins from cytoplasmic vesicles to plasma membrane
- GLUT 4 proteins are the insulin responsive glucose transporters
- they are in the skeletal muscles and adipose tissues (major sites of nutrient storage
- requires insulin!!
describe GLUT 1
- insulin independent
- found in CNS, RBCs
- high affinity for glucose
- ensures contant supply of glucose to essential cells (brain cells, RBC)
describe GLUT 2
- facilitated insulin independent glucose transport
- primarily in the liver, pancreatic beta cells, kidney and small intestine
- low affinity for glucose, allows bidirectional transport
- facilitates glucose uptake after meal for storage
-participates in glucose sensing by beta cells and triggers insulin secretion
explain how insulin influences metabolism of carbohydrates in muscles
- promotes muscle glucose uptake by GLUT4
- increases glycogen synthase activity (stimulates glycogenesis)
explain how insulin influences carbohydrate metabolism in the liver
- glucose uptake by GLUT2
- inactivates liver glycogen phosphorylase to inhibit glycogenolysis
- increases glycogen synthase activity, stimulating glycogenesis
- promotes conversion of glucose into fats
- inhibits glyconeogenesis
describe how insulin impacts fat metabolism
- inhibits hormone sensitive lipase
- stimualtes de novo lipogenesis (production of fatty acids from glucose)
- promotes lipoprtein lipase (increases delivery of fatty acids into tissues)
discuss how insulin influences protein metabolism
- increases amino acid uptake by tissues
- increases the rate of transcription and translation
- inhibits catabolism of proteins
- depresses the rate of gluconeogenesis within the liver (inhibits enzymes and lowers supply of amino acids from tissues
what is glucagon
- secreted by alpha cells of the islets of langerhans
- peptide hormone
- synthesised as preproglucagon
- rapidly converted into glucagon
- short plasma half life :5-6 minutes
- metabolised in the liver and kidneys
what are the actions of glucagon
- generally a catbolic hormone
- primary site of action is liver
- metabolic processes respond to: glucagon increasing in concentration and insulin decreasing in concentration
- insulin/glucagon ration determines actions
- alpha cells primarily respond to a low blood glucose level
how is glucagon secreted
- inhibited by high blood gluose levels
- stimulated by high amino acid levels
- protects from post prandial hypoglycemia after protein rich meal
