Lecture 8 - Endocrine

Question 1

What is diabetes?

Answer 1

The inability to regulate plasma glucose within normal range

Question 2

What does absolute or relative insulin deficiency lead to?

Answer 2

Hyperglycaemia Glycosuria (glucose in the urine) Polyuria (production of large volumes of dilute urine) Polydipsia (intense thirst)

Question 3

What is diabetic level?

Answer 3

> 7.8mmol/L

Question 4

What is postprandial level?

Answer 4

> 11.1 mol/L

Question 5

What are two types of diabetes?

Answer 5

Insulin-dependent (autoimmune) Non-insulin dependent (obesity)

Question 6

What does diabetes regulate?

Answer 6

Metabolism of fat

Question 7

What are digestive food capable of stimulating?

Answer 7

B cells and releasing insulin

Question 8

What is an example of GIT hormone and what does it do?

Answer 8

Incretins and it is responsible for stimulating B cells

Question 9

What can sulfonylureas be used to do?

Answer 9

Elevate the release of insulin from B cells

Question 10

What is an example of insulin receptor?

Answer 10

Tyrosine kinase

Question 11

What happens when insulin binds to its receptor?

Answer 11

Dimerisation of the receptor

Question 12

How is glucose taken up?

Answer 12

Recruitment of glucose transporters and insertion of these into membrane of target cells

Question 13

What happens when there is a desensitised non-functioning receptor?

Answer 13

No recruitment of glucose transporters and hence constantly elevated levels of blood glucose Glucose won’t be able to be processed or stored

Question 14

What are the many effects of intermediaries of kinases that effect glucose utilisation?

Answer 14

Increased formation of glycogen, protein and fat Increased uptake of glucose Increased utilisation of glucose Decrease formation of glucose from glycogen, fat and protein

Question 15

What are type I diabetes?

Answer 15

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

Question 16

What are consequences of type I diabetes?

Answer 16

Lipolysis is Increased - production of ketone bodies from fatty acids Ketonuria and metabolic acidosis - bodily fluid become hypertonic Cellular dehydration (hyperosmar coma)

Question 17

What is type II diabetes?

Answer 17

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

Question 18

What are the long term complications of diabetes?

Answer 18

Effect upon heart and coronary circulation Neuropathy - nerve damage (mobilisation of lipids within body)

Question 19

Why are diabetics prescribed statins?

Answer 19

Regulate blood lipids

Question 20

How is insulin normally administered?

Answer 20

Injection

Question 21

What are the types of insulin?

Answer 21

Rapid acting to long-acting

Question 22

What does onset mean

Answer 22

Length of time before insulin reaches the bloodstream

Question 23

What does peak mean?

Answer 23

Time period when insulin is most effective

Question 24

What is duration?

Answer 24

How long insulin works for

Question 25

What happens when 2 forms of insulin are combined?

Answer 25

Correctly mimic what is happening in unaffected individual

Question 26

What are the several causes of Hypoglycaemia?

Answer 26

Insulin dose is too large Individual has missed a meal Physical exertion

Question 27

What are the symptoms of Hypoglycaemia?

Answer 27

Mental confusion Palpitations Sweating Trembling Coma

Question 28

What are the treatment of Hypoglycaemia ?

Answer 28

Glucagon administration Rapid glucose administration

Question 29

What are the immune-mediated responses of Hypoglycaemia ?

Answer 29

Insulin allergy Immune mediated insulin resistance

Question 30

What are the consideration before pharmacological intervention?

Answer 30

Dietary modification or lifestyle changes can reduce the severity of the diabetes being suffered from

Question 31

What does level of glycated haemoglobin correlate with?

Answer 31

Individual overall health status in terms of severity of diabetes

Question 32

How can you risk the risk of many complications associated with chronic conditions?

Answer 32

Lower glycated haemoglobin and control type II diabetes

Question 33

Lowering HbA1c

Answer 33

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

Question 34

What is Oral hypoglycaemic ?

Answer 34

Anti-diabetic drug designed to help people with type II diabetes to manage their condition

Question 35

What can alpha-glucosidase inhibitor affect?

Answer 35

Absorption of food including glucose across the gut Affect upon glucose levels

Question 36

What does hepatic glucose overproduction do?

Answer 36

Affect overall liver function Gluconeogenesis, lymphatic glucose production from stored fats or complex carbohydrates

Question 37

What are the major sites of action of oral Hypoglycaemics?

Answer 37

Beta-cell dysfunction Insulin resistance Glucose absorption Hepatic glucose overproduction

Question 38

Biguanides -metformin

Answer 38

Do not require functioning beta-cell for their therapeutic effect

Question 39

What is the postulated mechanisms for Biguanides?

Answer 39

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

Question 40

What is mechanism of action of sulphonylureas?

Answer 40

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

Question 41

What does Glinides do?

Answer 41

Modulate B-cell insulin release (regulate K+ efflux via KATP) Controls post-prandial Glucose Increases (restores initial insulin secretion)

Question 42

What is Thiazolidinediones (Glitazones) ?

Answer 42

Insulin sensitizers Act on peroxisome proliferator-activated receptor Gamma

Question 43

What is incretin?

Answer 43

Endogenous compounds that can promote insulin release

Question 44

What are examples of GLp-1 agonists ?

Answer 44

Exenatide Liraglutide

Question 45

What are examples of dipeptidyl peptidase IV inhibitors?

Answer 45

Vildagliptin Sitagliptin

Question 46

What is an example of pramlintide ?

Answer 46

Injectable amylin analogue