LECTURE 25-26: ENDOCRINE Flashcards
Describe the biochemical function of insulin and glucagon
- Insulin - A polypeptide hormone, produced by b-cells of the pancreas
o Primary function is to trigger the absorption of glucose from the blood
Into the liver, skeletal muscle and fat tissue - Glucagon - A polypeptide hormone, produced by a-cells of the pancreas
o Primary function is to trigger the release of glucose into the blood
From the liver via gluconeogenesis and glycogenolysis
Type I
- Deficiency of insulin
- Metabolism is affected in liver, muscle and adipose tissue
Type II
- Insulin produced, body does not respond to it
- Metabolism is affected in liver, muscle and adipose tissue
Diabetes treatment
1) insulin and insulin analogues
2) oral hypoglycaemic drugs
3) a-glucosidase inhibitors
4) gastrointestinal hormones
Describe the mechanism of action of a-glucosidase inhibitors
- Treatment aims to reduce blood glucose levels
a-glucosidase inhibitors - Carbohydrates are broken down to monosaccharides by enzymes in the digestive system
- These include a-glucosidases
- AGIs inhibit the action of these enzymes
- Carbohydrates cannot be broken down and therefore are not absorbed
- AGIs are small carbohydrates that act as competitive inhibitors of these enzymes
- Common AGIs:
- Acarbose
- Miglitol
- Voglibose
Outline the key aspects of insulin use as a therapeutic
- Insulin therapy is the only treatment option for Type I diabetes
a. Lifetime therapy
b. Accompanied by change of diet to low fat, low sugar diet - Insulin would be broken down in the digestive tract if taken orally
c. Must be injected
d. Can also be delivered via pump
Describe the mechanism of action of insulin secretagogues
- Promote insulin release from the b-cells of the pancreas
- Bind to and close ATP-sensitive K+ channels on b-cells
o Depolarises the cells and opens Ca2+ channels
o Triggers fusion of insulin granules with cell membrane
insulin secretagogues are divided into ____ and ____ with the examples ____ and ____, respectively
Sulfonylureas and Meglitinides
tolbutamide and repaglinide
Sulfonylureas vs. Meglitinides
meglitinides have faster onset and short duration of action than sulfonylureas
Describe the mechanism of action of insulin sensitisers
- Improve the response of target cells to insulin
- Do not increase release of insulin from the pancreas
- Can be used in treatment of Type I or II diabetes
- Requires insulin treatment in Type I diabetes
examples of insulin sensitisers
Biguanides and Thiazolidinediones
Thiazolidinediones
- Mechanism of action is activation of PPARs
o Peroxisome proliferator-activated receptors - PPARs are nuclear receptors that act as transcription factors
o Modify transcription of target genes - Regulates lipid and glucose metabolism
o Increases insulin sensitivity of adipose tissue, liver and skeletal muscle - Used in treatment of Type II diabetes
Thiazolidinediones eg
pioglitazone, rosiglitazone
Describe the basis of pituitary disorders
- most cause by tumor
- lead to excess or deficient production
Describe the biology of ACTH and associated disorders
- Primary function is to trigger production and release of cortisol and androgens from adrenal gland
- Deficiency of ACTH can lead to secondary adrenal insufficiency
o Treatment involves repletion of deficient adrenal hormones
o e.g., prednisone, dexamethasone - Excess ACTH can lead to excess cortisol (Cushing’s syndrome)
o Treatment involves surgery and cortisol blocking medication (not particularly effective)
o e.g., ketoconazole, mifepristone
Describe the biology of growth hormone and associated disorders
- Peptide hormone that stimulates growth and cell reproduction
- Released from anterior pituitary
o Bind to cell surface receptors, e.g., MAPK, JAK-STAT
Excess growth hormone (acromegaly)
* Pituitary tumour leading to increase GH levels
* Thickens the bones of the jaw and digits
* Can lead to muscle weakness and pressure on nerves
* If such a tumour occurs during childhood, can cause gigantism
* Treatment includes surgery and GH antagonists (e.g., pegvisomant)
* Can use octreotide (somatostatin agonist) or bromocriptine (dopamine agonist) – both block GH secretion
Growth hormone deficiency
* Effects of GH deficiency depend on age
* In children, it can cause reduce growth and short stature
* In adults, it can increase osteoclast activity, leading to weak bones and osteoporosis
* Can also cause increased fat mass and decreased muscle mass
* Treatment is by GH replacement therapy
Describe the biology of vasopressin and associated disorders
- Peptide hormone from the posterior pituitary
- Two main functions:
o Increases water reabsorption from the kidneys
o Constricts arterioles - Overall effect is to raise blood pressure
- Very similar chemical structure to oxytocin
Diabetes insipidus - Disorder characterised by excessive dilute urine and increased thirst
- Central DI due to insufficient vasopressin production
- Nephrogenic DI due to kidneys not responding to vasopressin
- Effect is the same – water not reabsorbed
- Risk of dehydration
- Treatment for central DI
- Desmopressin: synthetic vasopressin
- Typically delivered orally or via nasal spray
- Can cause hyponatremia
- Treatment for nephrogenic DI
- Treatment focuses on causes, e.g., excess calcium
- Uses diuretics, hydrochlorothiazide and amiloride
- This helps restore normal ion balance and hence kidney function
Describe the biology of the thyroid and its hormones
Thyroid hormones
* Primary role is to increase basal metabolic rate
Thyroxine (T4)
Triiodothyronine (T3)
* The main active thyroid hormone
Outline the treatment options available for hyperthyroidism
Anti-thyroid drugs
- Inhibit the action of thyroperoxidase
- Enzyme adds iodine to thyroglobulin to make T4
- Examples: carbimazole, methimazole, propylthiouracil
b-blockers
- Inhibits action of thyroxine deiodinase
- T4 cannot be converted into T3
Radioiodine
- Iodine-131 (131I) is used to reduce the activity of a hyperactive thyroid
- Considered more effective than medication
