Pancreas and diabetes Flashcards
What % of the pancreas is endocrine tissue?
1%
What are the parts of the pancreas?
head
neck
body
tail
What polypeptide hormones are secreted by the pancreas? (7)
- insulin
- glucagon
- somatostatin (GHIH)
- pancreatic polypeptide
- ghrelin
- gastrin
- vasoactive intestinal protein
What cell types are insulin, glucagon, somatostain, ghrelin gastrin and pancreatic peptide secreted from?
insulin: beta cells
glucagon: alpha cells
somatostatin: delta cells
PP: PP cells
ghrelin: e cells
gastrin: G cells
What effects does insulin have?(5)
- in liver stimulates glycogenesis (stimulates glycogen synthase, inhibits glycogen phosphorylase)
- in adipose and muscle stimulates GLUT4 to open and so glucose can come in so lowers blood glucose
- in muscles it increases AA uptake for protein synthesis
- in liver decrease AA breakdown
- in adipose inhibits hormone sensitive lipase so less lipolysis
What effects does glucagon have? (3)
- glycogenolysis and gluconeogenesis in liver
also lipolysis which leads to ketone production
what is the renal threshold for glucose and what does this mean?
> 10 mmol/L
glucose cannot all be reabsobed so some will be lost in urine leading to glycosuria
It can decrease in pregnancy and increase in elderly
What is the normal plasma conc of glucose ?
3.3- 6 mmol/L (7-8 after meal)
how long does insulin and glucagon last in blood? (half life)
5 mins half life
Describe the creation of insulin
- synthesised into RER as preproinsulin
- signal sequence cleaved makes it proinsulin
- taken to golgi where C peptide cleaved, 2 disulfide bonds between A and B peptide
- insulin and c protein held in vesicles near cell surface ready for release when stimulated
Describe the stimulation of insulin to be released
- high glucose means more into cell via GLUT2
- means more metabolism and so more ATP
- ATP inhibits the ATP sensitive K+ channel
- less K+ efflux
- membrane depolarises
- voltage gates Ca2+ channels open
- Ca 2+ causes insulin release
Describe the structure of the tyrosine kinase insulin receptor
- a dimer
- 2 identical a and 2 b subunits
- disulfide bond between each a and B subunit
- a subunit on exterior of membrane
- B subunit transmembrane
What is released when amino acid conc in blood goes up?
both glucagon and insulin are released
- possibly because body thinks its starving (muscle breakdown) but also eating meat (?)
Describe the structure of glucagon
a long peptide of 29 AA with no disulfide bonds
What causes 90% of type 1 diabetes mellitus?
- 90% is auto immune destruction of the B cells by auto antibodies such as (ICAs, IAAs, IA2s and GADs)
What are the common signs and symptoms of type 1 diabetes mellitus?
- polyuria
- polydipsia (increased thirst)
- weight loss
- tiredness
- acetone on breath
- sweet smelling wee
- lethary
In what age group does type 1 diabetes present and over what time period do symptoms progress?
usually in young pts under age of 30
- symptoms deteriorate over weeks to months before presentation
How does type 1 diabetes lead to ketoacidosis and describe and explain the signs and symptoms (6) of ketoacidosis
- glucose cant be utilised as no insulin
- lipolysis as need energy that can be used + no insulin to stop it
- fatty acids converted to ketone bodies in liver
- leads to excretion of ketones in breath and urine
- also hyperventilation due to acid in blood–> more breathing= more Co2 removal so lower ph
- Nausia and vomiting to remove acid from GI
- abdo pain (dunno why)
- eventually coma
What tests can be done to test for diabetes?
- urine dip stick- look for glucose and ketones in urine
- HbA1c- glycation of Hb due to long term high glucose
- fasting glucose above 6mmol/L
- normal glucose on finger prick above 11mmol/l
How is type 1 diabetes managed?
- subcutaneous insulin injections after meals
- education about when and how to inject
- eduction on hypos when dont eat for long time–> need to carry sweets with them
- self monitoring of blood glucose
- check ups on feet, Bp, kidneys and eyes
What are the macrovasculature (3) and microvasculature (5) complications of diabetes as a result of high blood glucose causing vasculature damage?
Macro:
- risk of stroke
- risk of MI
- poor circulation to feet
Micro:
- diabetic eye disease (changes in lens due to osmotic effect of glucose)- blurred vision
- retinopathy (damage to blood vessles in eye leads to blindness)
- nephropathy (damage to glomeruli)
- neuropathy (peipheral nerve damage, leads to loss of sensation)
- diabetic foot (poor blood supply and nerve supply leads to foot ulcers)
What is type 2 diabetes?
insuffiecient insulin production due to an aquired insulin resistance (the balance of resistance vs low production may vary person to person)
in what age group does type 2 diabetes occur?
older (> 30/40)
What symptoms differentiate type 1 and type 2 diabetes?
- type 1 has high ketones, type 2 doesnt (type 2 insulin still has some effect to surpress lypolysis)
- not usually weight loss in type 2
- older ppl generally get type 2
How is type 2 diabetes managed? (5)
- primarily exersize and weightloss as it can be reversed by this to an extent
- metformin (inhibits gluconeogenesis, so helps reduce blood glucose)
- sulponylureas sometimes given - inhibits atp sensitive K+ channels so more insulin released
- inulin - B cells often give up on secreting it towards later stages
- bariatric surgery
What else can cause excessive thirst (polydipsia) and peeing (polyuria)?
- hypercalacaemia
- diabetes insipidus (increased ADH release)
- psychotic polydipsia (more than 3L water per day, washes out renal conc mechanism so wee lots)
Describe the symptomatic presentation of type 2 diabetes (most found on normal checks)
- overweight/ obese
- inactive
- > 40 yrs old
- irritable
- tired
- down
- thrush infections
- weight loss (unusual)
- increased weeing and drinking
Whats the difference between glycation and glycosylation?
glycation is non enzymatic
What are normal and diabetic levels of HbA1c?
normal- 4-6%
above 10% is diabetic
What receptor type does glucagon act on?
GPCRs
- PKA phosphylates target enzymes
What can C peptide be used for?
measure endogenous insulin secretion levels
What causes hypo and hyperglycaemia?
hypo- glucose dropping- may be due to insulin given but they miss a meal, exersize ect
hyper- high glucose- may eat high fat meal and not give insulin
What are the effects of hyperglycaemia?
- glucosuria
- polyuria
- dehydration
- confusion
- polydipsia
- blurred vision
- headaches
- fatigue
What are the effects of hypoglycaemia?
- shakey
- confusion
- sweaty
- anxious
- hungry
- irritable
- headache
What is metabolic syndrome?
having a cluster of the biggest risk factors for cardiovascular disease as a result of a sedentary lifestyle
What risk factors are included in metabolic syndrome? (4/5)
- diabetes (or raised plasma glucose)
- abdominal obesity
- high LDL or low HDL
- high BP
What causes metabolic syndrome?
- insulin resistance
- central obesity
- genetics
- inactivity
- ageing
What causes insulin resistance to develop in type 2 diabetes? (5)
- central obesity
- muscle and liver fat deposition
- elevated free circulating fatty acids may antagonise the insulin receptor
- inactivity
- genetic influences
