18/5 Insulin Flashcards
When insulin is being made its synthesised as?
Proinsulin
What class of drug is insulin?
Polypeptide hormone
Explain the process of insulin secretion
Rise in blood glucose (5-6mM) detected by GLUT2 in beta cell
-rise in ATP
- inhibits k+ ATP channel
- depolarisation of cell membrane
- activates ca2+ influx into cell
- stimulates insulin secretion & synthesis
- insulin containing granules released
Role of insulin:
Glycogenesis
Gluconeogenesis
Glycolysis
Lipolysis
Lipogenesis
Amino acids
Glycogenesis- increases glycogen production in muscle and liver
Gluconeogenesis - decreases glucose production in liver
Glycolysis - increase ATP production in liver and adipose tissue
Decreases lipolysis
Increases lipogenesis and esterification of fatty acids in liver and adipose tissue
Decreases breakdown of amino acid in liver and increases uptake & protein synthesis in muscle, liver and adipose tissues
Normal blood glucose
5-6 mmol
Lack of secretion of insulin- what type of diabetes ?
Type 1 diabetes
Loss of responsiveness to insulin - insulin resistance. What type of diabetes?
Type 2 diabetes
How does cow and pig insulin vary from human insulin?
Pig- varies by a single amino acid
Cow- varies by 3 amino acids
How can you change the ADME characteristics of insulin?
Altering the amino acid sequence of insulin
List 2 insulin replacements
- Rapid acting insulins (bolus insulins)
- Long acting insulins ( background insulins)
Define lispro
Lysine and proline residues reversed on the C terminal end of the beta-chain
Define aspart
Substitution of a proline for aspartic acid
When are bolas insulin used?
For injection after eating (post prandial) or in pumps
Role of bolus insulins
Lispro + aspart: prevent the formation of insulin dimers= more effective at stimulating the receptor
Background insulins have undergone various modification to?
- precipitate in the subcutaneous tissue allowing for slow release
- increase affinity for serum albumins which extend their life span in serum
List examples of background insulin
Degludec
LY2605541 and Lantus
Detemir
Advantages of long acting insulin
Active in the body for more man 24 hours so patients can maintain good blood sugar
Effective for basal insulin therapy for T1 + T2 diabetes
Reduced hypoglycaemia during the night and reduced severe hypoglycolemia
Disadvantages of background insulin
Can cause hypoglycaemia in up to 40% of patients
Some people exhibit allergic reactions
Insulin secretagogues are usuallyprescribed for what type of diabetes? And why?
Type 2
Need active pancreative beta cells, T1 diabetes don’t have active beta cells
Secretagogues stimulate release of?
Insulin from beta cells
2 classes of insulin secretagogues
Sulphonylureas and meglitinide
Examples of meglitinides
Repaglinide
Nateglinide
Examples of sulfonylureas
1st gen: chlorpropamide
2nd generation: more potent
Glimepiride
Glipizide
Glyburide
How do sulphonylureas work?
Stimulate release of insulin
-Act on the sulphonylurea receptor (SUR)
Binding closes linked ATP sensitiveK+ channels
Use k+ infux=depolarisation of beta cell membrane
Ca 2+ channels open= influx of Ca2+
Translocation + exocytosis of secretary granules of insulin
How do glinides differ from sulphonylureas?
Similar route of action, rapid onset $ short duration of action but have:
- weaker binding affinity
- faster dissociated from the SUR1 binding site
Advantages of insulin secretagogues
Oral tablet form
Flexible but multiple dosing (before meals)
Nateguinide and repaglinide not widely prescribed but provide alternative to a sulfonylurea for people with erratic lifestyles or irregular meal patterns (shift workers)
Example of glinides
Meglitinide
Repaglinide (prandin)
Nateglinide (starlix)
