ENI - Pancreas Flashcards
Describe the exocrine pancreas
- Large component
- Secretes digestive enzymes
- Secretes bicarbonate
- Digestive enzymes include: trypsin, carboxypeptidase, lipase, phospholipase, amylase, ribonuclease, deoxyribonuclease
Describe the endocrine pancreas
- Concentrated in islets of Langerhans (1-2% of pancreas)
- 3 cell types
- Beta: insulin (60-70%)
- Alpha: glucagon (20-25%)
- Delta: somatostatin (10%)
- Also pancreatic polypeptide, ghrelin, vasoactive intestinal peptide (VIP) secretin, motilin and substance P
Describe somatostatin
- Produced by hypothalamus (PVN), stomach, intestine, pancreas
- Paracrine function
- Suppresive to insulin and glucagon secretion by local beta and alpha cells
Describe the synthesis of insulin
- Peptide hormone
- First: preprohormone
- Converted to prohormone (proinsulin)
- Have intracytoplasmic pool of proinsulin waiting for relase
- Secretion involves production of insulin from proinsulin
- Removal of C-peptide connecting 2 polypeptide chains which make up insulin (alpha and beta chains)
- These chains are connected by 2 disulphide bonds
Describe the secretion of insulin
- From beta cells
- Involves remoal of C-peptide from proinsulin
- Enters veins, into portal system, to liver, acts on liver first, then rest enters general circulation
- 3 mechanism of regulation
Describe the degradation of insulin
- In liver
- Within target cells after receptor binding
- Involves cleavage of 2 disulfide bonds
What are the 3 mechanisms of insulin secretion regulation?
- Nutrients
- Gastrointestinal hormones
- Autonomic nervous system
Outline how nutrients regulate insulin secretion
- Glucose and amino acids
- insulin secreted when these are high
- Action of insulin is to promote formation of storage molecules
Outline how gastrointestinal hormones regulate insulin secretion
- Incretins
- e.g. gastric inhibitory pepide (GIP and glucagon like peptide (GLP-1)
- Promote release of insulin (as incretins are relased at feeding want to use nutrients in storage moleucles)
Outline the autonomic nervous system regulation of insulin secretion
- Parasympathetic stimulates via vagus, increases gastrointestinal motility and digestion, higher insulin after feeding
- Sympathetic inhibits, direct innervation, indirect responses via adrenaline, stress response = hyperglycaemia, insulin secretion and action inhibited
Outline the mechanism of release of insulin
- GLUT2 transporters allow glucose into beta cell
- Phosphotylation of glucose by glucokinase, traps glucose in cell
- Increase in ATP production
- Inhibits ATP-sensitive potassium channels
- Increased intracellular potassium concentration leads to depolarisation
- Voltage-gated calcium channels activated
- Influx of calcium triggers exocytosis of insulin
What type of hormone is insulin?
Water soluble peptide hormone
What signal transduction pathway is used by insulin?
Tyrosine kinase
What are the cellular actions of insulin binding to its receptor?
- Activates tyrosine kinase signal transduction pathway
- Tyrosine kinase mediated signalling system promotes glycogen synthesis and other storage activities
- Movement of GLUT4 to memrbane so can be a receptor for glucose
Describe the GLUT4 receptors
- Insulin stimulates translocation of GLUT4 proteins
- From cytoplasmic vesicles to plasma membrane
- Insulin responsive glucose transporters
- In skeltal muscle and adipose tissue are major sites for nutrient storage
Explain the actions of insulin on carbohydrates and muscle
- Promotes glucose uptake via GLUT4
- Increases glycogen synthase activity, stimulatin glycogenesis
- Need glycogen as dotred form of energy
Explain the actions of insulin on carbohydrates and the liver
- No GLUT4, instead GLUT2 so insulin no effect on glucose uptake
- Metabolic efects instead
- Inactivates liver glycogen phosphorylase, inhibiting glycogenolysis
- Increases glycogen synthase activity, stimulating glycogenesis
- Promotes conversion of glucase into fats, de novo lipogenesis
- Inhibits gluconeogenesis
Explain the actions of insulin on the brain
- No GLUT4 in the brain, no effect on glucose uptake
- Insulin-independent GLUT1 transporter
- Except, need insulin for glucose uptake in satiety and appetite centres of hypothalamus
- Without insulin, no detection of glucose and so no signal for satiety
Explain the actions of insulin on fat metabolism
- inhibits HSL, decreasing lipolysis
- Stimulates de novo lipogenesis
- Excess gucose increases TCA cycle intermediates, activates acetyl CoA carboxylase, forms malonyl CoA (fat precursor)
- Increases fat delivery to tissues
Explain the actions of insulin on protein metabolism
- Increases AA uptake in tissues
- Increases rate of transcription and translation
- Inhibits catabolism of proteins
- Depresses rate of gluconeogenesis within liver by inhibiting enzymes and lowering supply of AAs from tissues (e.g. muscle)
Desribe glucagon
- Alpha cells
- Peptide hormone
Outline the synthesis of glucagon
- Preproglucagon
- Rapid conversion to glucagon
Where is glucagon metabolised?
- Liver and kidneys
- Short plasma half-life 5-6 minutes
Describe the actions of glucagon
- Catabolic
- Liver main site of action
- Metabolic processes repond to increasing glucagon and decreasing insulin
- Ratio of I and G determines actions
- Alpha cells respond to low blood glucose
- Aims to maintain blood glucose between meals
- activated during negative energy balance
Describe glucagon in the liver
- Stimulates glycogenolysis and gluconeogenesis
Describe glucagon secretion
- Inhibited by high blood glucose levels
- Stimulated by high amino acid levels e.g protein rich meal to promote gluconeogenesis as insulin would lead to hypoglycaemia as little cabohydrates present
What are the effects of hyperinsulinaemia on blood
a. glucose
b. glycogen
c. amino acids
d. fatty acids
e. triglycerides
A. Lowers B. Increases C. Lowers D. Lowers E. Increases
What is the effect of insulin on glucose-6-phosphatase? (give increased or decreased enymatic activity, the metabolic process it is involved in and whether the process is stimulated or inhibited)
- Decreases enzymatic activity
- Involved in gluconeogenesis
- Process inhibited
What is the effect of insulin on glycogen phosphorylase? (give increased or decreased enymatic activity, the metabolic process it is involved in and whether the process is stimulated or inhibited)
- Descreases enzymatic activity
- Involved in glycogenolysis
- Process inhibited
What is the effect of insulin on glycogen synthase? (give increased or decreased enymatic activity, the metabolic process it is involved in and whether the process is stimulated or inhibited)
- Increased enzymatic activity
- Involved in glycogenesis
- Process stimulated
What is the effect of insulin on hormone sensitive lipase? (give increased or decreased enymatic activity, the metabolic process it is involved in and whether the process is stimulated or inhibited)
- Decreased enzymatic activity
- Involved in lipolysis
- Process inhibited
What are insulinomas?
Tumours of beta cells of Islets of Langerhans
What are the signs of hypoglycaemia in the central nervous system?
- Sweating
- Palpitations
- tremulousness
- Anxiety
- Hunger
- Dizziness
- Confusion
What are the signs of hypoglycaemia in the musculoskeletal system?
- Weakness
- Tremors
- Ataxia
- Generalised focal seizures
How are insulinomas diagnosed?
- High serum insulin
- High C-peptide
- Resting glucose low
How does cortisol (prednisolone) administration lead to an increase in blood glucose?
- Antagonises insulin
- Reduces uptake of glucose into cells (reduced translocation of GLUT4 transporters to cell membrane)
- Reduces lipogenesis
- Glycogenesis
- Stimulates gluconeogenesis and glycogenolysis
- Decreases peripheral use of glucose
