Name the 3 important nomenclature?
Glucose: as a sugar
Glucagon: hormone acts to stimulate glucose production
Glycogen: polymer of glucose
Hormones producing during starvation/fasting?
Glucagon is a peptide hormone that is released from the pancreatic alpha-cells when blood glucose drops.
Stimulates glucose production and secretion from the liver and glucogen breakdown in muscle.
Hormones produced after food or nutrient intake?
Insulin is a peptide hormone that is released from the pancreatic beta-cells when blood glucose rises.
Induces glucose removal from blood and storage.
What is the normal blood glucose level?
What organ in the body needs a constant supply of glucose?
Type 1 Diabetes?
Characterised by the failure to synthesis or secrete insulin.
Autoimmune destruction of beta cells.
Type 2 diabetes cause?
Caused by target tissues becoming resistant to the effects of inuslin
What are the minor forms of diabetes?
MODY and gestational.
What is the major risk factor for type 2 diabetes?
3 Treatments for type 1 diabetes?
Islet transplants and stem cells.
What is the difference in structure for the proinsulin and insulin?
Proinsulin contains C peptide chain as well as alpha and beta chain (With disulphride bonds between them).
Cleaved with PC2 and 3 to make insulin (Without the C peptide chain)
What are the clinical uses of insulin?
Life saving for type 1 diabetes.
Last option for type 2: for type 2 diabetes the body still produces insulin but the target cells do not respond to this insulin. Therefore the beta cells try to compensate by producing more insulin. Eventually this destroys the beta cells and insulin is needed.
Human insulin is produced how for clincal use?
Produced by recombinant technology
Replaced bovine and porcine insulin preparations.
what is the danger of injecting insulin?
If you give too much: danger of hypoglucemia.
Is it a set insulin preparation or is there many?
There are many insulin prepartions.
Formulated to differ in their peaks and durations.
Name the 5 types of insulin preparations?
- Ultra fast/ ultra short acting
- Ultra long-acting.
Short acting ones are best straight after nutient intake.
How do they make insulin ultrafast and ultra-short acting?
example of a preparation?
The 20 and 21 amino acid (Lys and Pro respectively) are swapped over on the beta chain.
Affecting the stability of this insulin prepartion. Causing it to be short acting.
Rapidly acting insulin
Must be used with long-acting preparations.
Insulin glargine is an example of what kind of insulin preparation?
How does it vary in structure to normal insulin?
Its an ultra long-acting insulin
21st amino acid on the alpha chain is Gly and the 31 and 32nd amino acids on the beta chain are now ARG.
How successful has transplant been?
Few successful transplants.
Most had to return to insulin.
Additionally high cost: 3 donors per patient (have to be dead)
Still on drugs: swap insulin for immunosuppressants.
What are stem cells?
Still havent decided their fate
Can be induced into any cell fate (including beta-cells in the pancreas)
How could stem cell therapy be used for the treatment of type 1?
Stem cells could be removed from the patient and treated in a culture to becomes beta-cells of the pancreas.
Injected back in.
Since the cells are the patients one: immunosuppressants are not required.
Current treatment for type 2 diabetes?
Exercise and diet control (reduce weight): first line of treatment.
Alpha-glucosidase inhibitors: stops the feeling of needing to eat.
Incretins: increase insulin production.
Sulfonylureas: Stimulates insulin production. Weight gain
Giltazones (TZDs): affects adipose function.
Biguanides: Insulin sensitiser.
Why is exercise the first treatment?
Utilises the glucose
Activates AMP kinase
What does AMP do?
Binds to and allosterically activate AMPK.
Competes to the same site as ATP (used to inactivate AMPK).
AMPK inhibits energy consuming processes.
Benefits of exercise?
Reduce type 2 diabetes.
Reduce obesity and therefore the risk of obesity related disease.
Why exercise is the first treatement and not drugs?
Exercise doesnt impact your life
Lots of drugs have to be taken and all at different times.
Drug interactions can occur (and side effects)
Biguanide class of compounds.
Insulin sensitiser (helps insulin to work)
Increases glucose uptake into liver while inhibiting glucose production.
Activate AMP kinase
Problems with metformin?
Only works in 50% of cases.
Side effect: can produce lactic acidosis.
Resistance can occur
Stimulate insulin secretion from pancreatic islets.
Regulate KATP channels.
Problems with Sulphonylureas (SURs)?
Danger of hypoglycemia
Bind to PPARgamma
Regulate transcription of many genes involved in metabolism of lipids and carbohydrate.
Mainly expressed in adipose.
Reduce blood glucose.
Storing excess glucose into fat.
Slow carbohydrate digestion
Problems with acarbose?
Gastrointestinal side effects.
Peptide produced by the salivary glands of the gila monster.
Regulate blood glucose- increasing insulin secretion from the pancreas.
Gastrointestinal peptides released into the circulation.
Breakdown the food more efficiently.
Act at specific receptors in the pancreatic beta-cells to increase insulin secretion (only when glucose is present)
Problem with incretins?
Half life is too short to be used clinically.
Degraded by DPP-IV.
Inhibit the SGLT2 receptor: used for the reuptake of glucose in the kidney.
Independent of insulin: low risk of hypoglycemia