Lecture 8 - Endocrine Flashcards
What is diabetes?
The inability to regulate plasma glucose within normal range
What does absolute or relative insulin deficiency lead to?
Hyperglycaemia Glycosuria (glucose in the urine) Polyuria (production of large volumes of dilute urine) Polydipsia (intense thirst)
What is diabetic level?
> 7.8mmol/L
What is postprandial level?
> 11.1 mol/L
What are two types of diabetes?
Insulin-dependent (autoimmune) Non-insulin dependent (obesity)
What does diabetes regulate?
Metabolism of fat
What are digestive food capable of stimulating?
B cells and releasing insulin
What is an example of GIT hormone and what does it do?
Incretins and it is responsible for stimulating B cells
What can sulfonylureas be used to do?
Elevate the release of insulin from B cells
What is an example of insulin receptor?
Tyrosine kinase
What happens when insulin binds to its receptor?
Dimerisation of the receptor
How is glucose taken up?
Recruitment of glucose transporters and insertion of these into membrane of target cells
What happens when there is a desensitised non-functioning receptor?
No recruitment of glucose transporters and hence constantly elevated levels of blood glucose Glucose won’t be able to be processed or stored
What are the many effects of intermediaries of kinases that effect glucose utilisation?
Increased formation of glycogen, protein and fat Increased uptake of glucose Increased utilisation of glucose Decrease formation of glucose from glycogen, fat and protein
What are type I diabetes?
Pancreatic B cells are destroyed by an auto immune T cell attack Complete inability to secrete insulin and ketoacidosis is a problem Apparent at young age Body can still respond to injection and introduction of insulin into the body
What are consequences of type I diabetes?
Lipolysis is Increased - production of ketone bodies from fatty acids Ketonuria and metabolic acidosis - bodily fluid become hypertonic Cellular dehydration (hyperosmar coma)
What is type II diabetes?
Insulin is often secreted as 50% of the B cells that remain active Peripheral resistance to insulin Common in population enjoying affluent life-style Increase with age and degree of obesity
What are the long term complications of diabetes?
Effect upon heart and coronary circulation Neuropathy - nerve damage (mobilisation of lipids within body)
Why are diabetics prescribed statins?
Regulate blood lipids
How is insulin normally administered?
Injection
What are the types of insulin?
Rapid acting to long-acting
What does onset mean
Length of time before insulin reaches the bloodstream
What does peak mean?
Time period when insulin is most effective
What is duration?
How long insulin works for
What happens when 2 forms of insulin are combined?
Correctly mimic what is happening in unaffected individual
What are the several causes of Hypoglycaemia?
Insulin dose is too large Individual has missed a meal Physical exertion
What are the symptoms of Hypoglycaemia?
Mental confusion Palpitations Sweating Trembling
Coma
What are the treatment of Hypoglycaemia ?
Glucagon administration Rapid glucose administration
What are the immune-mediated responses of Hypoglycaemia ?
Insulin allergy Immune mediated insulin resistance
What are the consideration before pharmacological intervention?
Dietary modification or lifestyle changes can reduce the severity of the diabetes being suffered from
What does level of glycated haemoglobin correlate with?
Individual overall health status in terms of severity of diabetes
How can you risk the risk of many complications associated with chronic conditions?
Lower glycated haemoglobin and control type II diabetes
Lowering HbA1c
Indicator of overall status of severity of diabetes Used as a marker of severity of diseased individual Glycosylated Hb test: determine how well a persons diabetes is being controlled over time
What is Oral hypoglycaemic ?
Anti-diabetic drug designed to help people with type II diabetes to manage their condition
What can alpha-glucosidase inhibitor affect?
Absorption of food including glucose across the gut Affect upon glucose levels
What does hepatic glucose overproduction do?
Affect overall liver function Gluconeogenesis, lymphatic glucose production from stored fats or complex carbohydrates
What are the major sites of action of oral Hypoglycaemics?
Beta-cell dysfunction Insulin resistance Glucose absorption Hepatic glucose overproduction
Biguanides -metformin
Do not require functioning beta-cell for their therapeutic effect
What is the postulated mechanisms for Biguanides?
Slow down Gastrointestinal tract absorption of glucose Increase the uptake of glucose into skeletal muscle Reduced glucagon levels Decrease hepatic gluconeogenesis Do not cause hypoglycaemia or simulate appetite
What is mechanism of action of sulphonylureas?
Block ATP-dependent K+ channels (K-ATP) Bind to ATP binding cassette Protein (ABC protein) which in turn causes the channel to close Closure of this channel results in B cell depolarisation, calcium entry and insulin release Strong correlation between affinity for this binding sire and clinical efficacy
What does Glinides do?
Modulate B-cell insulin release (regulate K+ efflux via KATP) Controls post-prandial Glucose Increases (restores initial insulin secretion)
What is Thiazolidinediones (Glitazones) ?
Insulin sensitizers Act on peroxisome proliferator-activated receptor Gamma
What is incretin?
Endogenous compounds that can promote insulin release
What are examples of GLp-1 agonists ?
Exenatide Liraglutide
What are examples of dipeptidyl peptidase IV inhibitors?
Vildagliptin Sitagliptin
What is an example of pramlintide ?
Injectable amylin analogue
