Control of Blood Glucose and the Endocrine Pancreas Flashcards
What is responsible for the maintenance of constant blood glucose?
Insulin
Where is insulin secreted?
Pancreas
Explain some functions of the liver
Has high capacity to take up glucose and can buffer increases in blood sugar concentration
Is the pancreas endo or excocrine?
Both, but mostly exocrine as it secretes digestive enzymes forming pancreatic juices into the gut
what is an endocrine gland?
secretes its products directly into the blood (e.g. hormones)
what is an exocrine gland?
secrets its products into ducts that lead to the target tissue (e.g. enzymes)
which parts of the pancreas constitute to the endocrine part?
the islets of langerhans
which parts of the pancreas constitute to the exocrine parts?
they all join up to form the pancreatic duct
what percentage of the islet do beta cells contribute to?
60%
what do the beta cells do?
secrete insulin
what do the alpha cells do?
secrete glucagon
what does the orginal transcript of insulin give?
pre-proinuslin
how does pre-proinsulin become proinsulin?
the signal sequence is cleaves off
how does proinsulin become insulin?
Chain C is removed in golgi apparatus
what type of vesicles is insulin packed into?
secretory vesicles
what is the threshold for insulin release?
5 mmol/L of glucose
what happens when blood glucose reaches 5 mmol/L?
anabolic actions of insulin stop and catabolic actions of glucagon take over
what regulates secretion of insulin?
mostly local (beta cells) but can be regulated by the sympathetic and parasympathetic mechanism
how do the beta cells know when the blood glucose rises?
beta cell membrane has GLUT 2 transporters so as blood glucose rises, it will diffuse into the cell DOWN gradient. it enters glycolysis and TCA cycle to give ATP. an ATP sensitive K+ channel in the membrane closes the channel = depolarisation so K+ cant diffuse out = more positive. The Depolarisation causes Ca2+ channels to open which act as intracellular messengers causing exocytosis of insulin vesicles
what type of messenger is ATP in the sensitive K+ channel?
Intracellular
what are the effects of insulin on the adipose tissue, skeletal muscle, and cardiac muscle?
glucose uptake and FFA/AA in adipose and muscle
How do the effects of insulin take place?
insulin binds to a receptor
what is the insulin receptor?
tyrosine kinase (inside membrane) gets activated by phosphorylation
what happens when the insulin receptor is phosphorylated?
IRS (insulin receptor substrate) is phosphorylated and causes activation of further downstream cell signalling pathways
what happens as a result of the cell signalling pathways of IRS?
there is insertion of glucose transporter (GLUT2) into cell membrane allowing uptake of glucose DOWN its gradient
- glycogen synthesis
- gene transcription
how does glucose get into cells?
GLUT transporters
What is GLUT 2?
Transporter in liver, kidney and pancreas allowing movement of glucose into pancreatic beta cells to stimulate insulin release
What are the details of GLUT 2?
low affinity transporter so works at constant rate of glucose flow over a range of concentrations
What is GLUT 4?
Transporter in muscle and adipose tissue, medium affinity for glucose important for removal of glucose from blood for storage. Insulin dependent uptake of glucose.
What is GLUT 1?
Brain transporter, high affinity
What is GLUT 3?
Brain transporter, high affinity
Where are the direct effects of glucagon?
on the liver, stimulating processes inhibited by insulin
what does glucagon stimulate?
glycogenolysis, gluconeogensis, ketogenesis
when hypoglycaemia persists, what does the sympathetic nervous system cause?
more release of glucagon in the liver and stimulation of catabolic processes in liver and other tissues
what suppresses the release of glucagon?
rise in blood glucose concentration
what stimulates release of glucagon?
amino acids
what are the direct effects of glucagon on the liver?
gluconeogenesis, glycogenolysis, ketogenesis (during starvation)
what type of molecule is glucagon?
peptide
how is glucagon synthesised?
starts of as pro-glucagon which gets cleaved into glucagon in the alpha cells of the pancreas
what happens to the pro-glucagon gene in the small intestine?
processed to give diff products e.g. GLP-1 (glucagon like peptide 1) which increases insulin secretion
what is GIP?
pro-gastrointestinal polypeptide. effect is to slow the rate of gastric emptying. makes insulin response to glucose stronger
what are incretins?
gut peptides
what are the three important signalling molecules?
- glucagon
- GLP-1 synthesised from the pro-glucagon gene released from gut cells with agonistic effect on insulin release
- GIP also has agonistic effect on insulin release
how do the three signalling molecules work together?
synergistically, release is stimulated in digestion. they prime the pancreas to be ready to deal with increase in blood sugar
what is the mechanism of how GLP1 and GIP work?
they bind to cell surface receptors on beta cells of the pancreas. their receptors have Adenyl cyclase activity inside increasing cAMP that has similar effect to ATP. this causes close of K+ channels so membrane gets depolarised and VG Ca2+ channels activated = exocytosis of vesicles. GLP1 and GIP amplify insulin secretion
how are GLP1 and GIP involved in glucose and fat response?
they are released in response, travelling in circulation to pancrease where they potentiate insulin secretion bringing down blood glucose
what does DPP-4 do?
degrade GLP1 and GIP peptides so arent in plasma for long
how have type II diabetes be reated with peptides?
long acting analogue GLP1 used or an inhibitor of DPP-4 so that the peptides work for longer to bring down blood glucose
how is the flow of fuels after an overnight fast?
- glucose is released into circulation
- free fatty acids released from adipose tissues, taken into muslce and forms ketone bodies in liver and TAG for recirculation as VLDLs
- gluceoneogensis
how is the flow of fuels after breakfast?
- glucose taken up into liver, muscle and adipose tissue with formation of glycogen and TAG
- amino acids taken up into liver and muscle
- lipolysis and proteolysis inhibited
- ketogenesis inhibited
what other hormones influence blood sugar?
Adrenaline
Growth Hormone
Cortisol
Thyroid
what blood glucose level is considered diabetic?
Above 7 mmol/L
What is the glucose tolerance test?
75g of glucose given and blood glucose measured 2 hours later/ Above 11.1 = diabetes as insulin wont be functioning properly
what are the metabolic disturbances of diabetes?
hyperglycaemia –> glycosuria –> osmotic disturbance = increased urine production = increased electrolyte loss –> acidosis
what is treatment for type I diabetes?
insulin replacement either with human insulin or islet cell transplantation
what is treatment for type II diabetes?
increase insulin secretion such as GLP-1
what are macro-vascular changes in terms of diabetic complications?
accelerated atherosclerosis due to the hyperglycaemia causing endothelial injur, platelet adhesion and plaque formation
what are micro-vascular changes in terms of diabetic complications?
structural changes in microvasculature leading to retinopathy, neuropathy and nephropathy
what is a good indicator of glycemic control?
glycosylated haemoglobin, less than 7% = good control
