If a drug is insulin dependent, what does this mean?
In order to have an effect, enough insulin must be present
Which drugs can be described as insulin independent?
- α-glucosidase inhibitors
- SGLT2 inhibitors
Name two drug classes involved in increasing insulins sensitivity
- Thiazolidinediones (glitazones)
As well as impacting insulin sensitivity, what other action do the biguanides and thiazolidinediones share?
Decrease hepatic gluconeogenesis
Which drugs will increase insulin secretion?
- Incretin mimetics
- DPP-4 inhibitors
Biguanides are insulin ____________
Biguanides are insulin dependent
Glinides are insulin ___________
Glinides are insulin dependent
α-glucosidase inhibitors are insulin ___________
α-glucosidase inhibitors are insulin independent
SGLT2 inhibitors are insulin _____________
SGLT2 inhibitors are insulin independent
DPP-4 inhibitors are insulin ______________
DPP-4 inhibitors are insulin dependent
GLUT4 is a glucose transport protein associated with which tissues?
(e.g. adipose and skeletal muscle)
Describe the process by which insulin is released
- Elevated BGL
GLUT2 allows entry of glucose to cell cytoplasm
- Glucokinase converts glucose to glucose-6-phosphate
- Glucose-6-phosphate is converted to ATP
ATP acts on KATP channel
- KATP channel closes and depolarisation of cell occurs
- Volages activated Ca2+ channels open
Ca2+ influx triggers exocytosis of insulin storage granules
Which drug class works by slowing glucose absorption from the GI tract?
During the insulin secretion mechanism, what exactly causes KATP channel to close?
The ratio of ATP:ADP
How many subunits make up the KATP channel?
Which two types of subunit are involved in the KATP channel?
To which subunit will ATP bind to in order to close the KATP channel?
Which substance can bind to the KATP channel in order to keep it open and to which subunit will it bind?
To which subunit will the sulphonylurea drug class bind to in the KATP channel and what is the useful effect of this?
This induces depolarisation leading to insulin release regardless of whether blood sugars are high or low
In order for the sulphonylureas to be of use what is required?
Pancreatic β cells
(this is why this drug class is useless in T1DM)
Why may the effect of the sulphonylureas decrease over time in a patient?
β cells decrease over time, even in T2DM
Give 4 examples of sulphonylureas
- Tolbutamide (1st gen - rarely used)
How do the sulphonylureas act?
Displacement of the ADP-Mg2+ from the SUR1 subunit causing closure of the KATP channel and subsequent depolarisation
Which risk is associated with sulphonylureas since they act independently to BGLs?
(BGLs may already be low when administered for example, which would reduce them further)
How can the sulphonylureas be administered?
What is the duration of action of the different sulphonylureas?
- Short acting - tolbutamide - 4-6 hours
- Long acting - glibenclamide, glipizide, gliclazide - 16-48 hours
Which type(s) of vascular risks associated with diabetes do the sulphonylureas reduce?
In which patients is hypoglycaemia a particular risk when taking sulphonylureas?
- Elderly (renal function decreases with age)
- Reduced hepatic or renal function
- Pregnant women
(N.b. Long acting agents pose a higher hypoglycaemic risk)
In a treatment algorithm, sulphonylureas will usually be _________ line therapy with __________
In a treatment algorithm, sulphonylureas will usually be second line therapy with metformin
(N.b Not in pregancy; they may also be used 3rd line with TZDs and metformin)
Sulphonylureas cause weight ________
Sulphonylureas cause weight gain