diabetes and its treatments Flashcards
(42 cards)
how is glucose stores in fat cells
insulin signals to make fatty acids
how is glucose stored at muscle and liver cells
insulin signals to make glycogen
what are the main organs involved in blood glucose homeostasis
pancreas, liver, muscle, and adipose tissue(insulin action)
what is insulin resistance
the incapability of insulin to initiate desired pathways
what is diabetes mellitus
an inability to control blood glucose concentrations
what are the different types of diabetes mellitus
type 1
type 2
gestational
monogenic
type 2 diabetes therapies
-reduce carb intake
-increase insulin secretion
-enhance insulin action
-increase glucose excretion
what its the ideal HbA1c level for. individuals with diabetes
48mmoll/mol (6.5%) or below
what are ⍺ - glucosidase inhibitors
-inhibit ⍺ - glucosidase enzymes in intestine
-prevent cleavage of oligosaccharides
-delay carb digestion
⍺-glucosidase inhibitor disadvantages
-the effects on blood glucose levels are modest
-undigested carbs pass into the large intestine
Flatulence and diarrhoea are major side
effects as colonic bacteria digest the
carbohydrates
what are drug is used to increase insulin secretion
Sulphonylureas
what are sulphonylureas
-Sulphonylureas and glinides
bypass glucose metabolism
-They bind to the β-cell
sulphonylurea receptor, SUR1
- This leads to closure of the
Kir6.2 pore → ↑ K+ efflux
→ membrane depolarisation
disadvantages of Sulphonylureas (and glinides)
- may cause hypoglycaemia (initiate insulin secretion at low glucose)
- may promote weight gain
- may be associated with increased risk of cardiovascular events (closure of Katp channels in cardiomyocytes)
what happens when glucose is administered orally as opposed to intravenously?
There is a significantly
enhanced insulin secretory
response to oral glucose
than to the same glucose
dose administered i.v
what are incretins
small peptide hormones released from the GI tract in response to food. intake that enhance the insulin secretory response to glucose by up to 60%
what are the 2 main incretins in humans?
glucose dependant insulinotropic polypeptide (GIP)
glucagon-like peptide-1 (GLP-1) (levels are lower in type 2 diabetes)
what is dipeptidyl peptidase 4 (DPP4)
GIP and GLP-1 inhibitors
-DPP-4 removes two amino acids from the N-termini of GLP-1 and GIP,
which renders them inactive
what is the T1/2 for GLP
2 mins
examples of GLP-1 with a longer half life being developed
Exenatide (Byetta)
Liragutide (Victoza)
what are the characteristics of Exenatide (Byetta)
- it has 50% amino acid homology with GLP-1 (bind GLP-1 receptors)
- introduced for clinical use in 2005
- 2h half live in vivo
- 39-amino acid synthetic version of extendin-4
what are the characteristics of Liragutide (Victoza)
-97 % sequence homology with GLP-1
- introduced for clinical trial in 2009 (EU) and 2010 (US)
- 13h half life (fatty acid
group prolongs the
action by allowing
it to bind to
albumin)
- Liraglutide is GLP-1
analogue that
contains a fatty
acid molecule and
a single amino acid
substitution
Activation of the GLP-1 receptor leads to:
Activation of adenyl cyclase (AC) which produces cAMP
* cAMP amplifies signals leading to insulin secretion
* Increase of insulin secretion but in a glucose-dependent
manner
Additional benefits of
GLP-1 receptor
agonists
- Decreases glucagon secretion
- Inhibition of appetite leading to weight loss
- Potentially increases pancreatic -cell mass
Exenatide/Liraglutide:
disadvantages
- must be administered intravenously
-nausea, vomiting and diarrhoea with initial use - kidney failure
- increased risk of gall bladder and biliary disease
- pancreatitis
- cost
