HALF DONE Drugs in Diabetes Flashcards
What are the hormone secreting cells of the pancreas, and what glucose regulating hormones do they secrete?
Islets of Langerhans:
- Insulin (β/B cells)
- Glucagon (α/A cells)
- Somatostatin (δ-cells)
What are three other glucose regulating hormones and their sources?
- Adrenaline (adrenal medulla)
- Glucocorticoids (adrenal cortex)
- Growth hormone (pituitary)
What is the normal range for glucose in the blood?
3.5 - 5.5 mmol/L
How does insulin, glucagon, adrenaline, glucocorticoids and growth hormone effect blood glucose?
Stimulated by high blood glucose, insulin decreases blood glucose.
The 4 others - glucagon, adrenaline, glucocorticoids and growth hormone - cause increased blood glucose levels.
Describe the 3 stimuli for the release of insulin.
Insulin release is stimulated by:
- Increased blood glucose
- Amino acids and FAs
- Peptide gut hormones (Incretins)
Once stimulus for insulin release is received, what happens next?
Insulin is stored in β cell granules as pro-insulin.
Protease cleaves pro-insulin, releasing insulin and a C-peptide
What are insulin’s metabolic targets and its action?
- CHO
- Fat
- Protein
CHO:
- Decrease gluconeogenesis and glycogenolysis
- Increase glycolysis and glycogenolysis
- Increase glucose uptake
Protein
- Increase AA uptake
- Increase protein synthesis
- Decrease protein breakdown
Fat
- Increase fat storage (lipogenesis)
- Decrease fat breakdown (lipolysis)
What type of receptor is the insulin receptor, and what is it’s major intracellular substrate?
Insulin receptor - receptor tyrosine kinase.
Insulin binding = dimerisation and auto-phosphorylation.
Major substrate = IRS-1
- Activates pathways to store energy
- Glucose into cells
- GLycogen synthase
What is diabetes mellitus and how can it present?
Diabetes mellitus is a group of disorders characterised by hyperglycaemia, caused by insulin deficiency.
Can present with:
- Polyuria, polydipsia, polyphagia
- Weight loss
- Poor healing and infections (e.g. foot ulcer)
What is the lab measurement diagnosis of diabetes and prediabetes?
Diabetes:
- Fasting blood glucose (FBG) >7.0mmol/L
- 2H after meal (OGTT) >11.1mmol/L
Pre-diabetes:
- FBG = 5.6 - 6.9 mmol/L
- OGTT = 7.8 - 11.0 mmol/L
What is glycated haemoglobin?
What levels are normal/diabetes/pre-diabetes?
Covalent modification of haemoglobin that occurs with raised blood glucose.
- Reflect long term measurement of glucose levels
- Normal = <6%
- Pre-diabetes = 6.0 - 6.4%
- Diabetes = >6.5%
What type of tissue effects occur in diabetes?
Catabolic effets:
- Opposite of what insulin does to CHO, fat and protein
- Increased blood sugar
- Increased blood lipids
- Increased protein breakdown
What are the two types of diabetes and their causes?
Type 1 DM
- ABSOLUTE insulin deficiency
- Auto-immune destruction of β cells
- Juveline onset
Type 2 DM
- RELATIVE insulin deficiency
- Peripheral resistance to normal insulin levels through progressive decrease in β cell function/mass
- Associated with obesity
What are the acute and chronic complications of diabetes?
Acute: Diabetic ketoacidosis
- Fats are used for energy, producting acetyl-CoA which is converted to ketones (decreased pH, hyperosmolar state)
Chronic: Vascular disease
- Macrovascular (HTN, heart attack, stroke)
- Microvascular (eyes, kidney)
What is the significance of vascular complications in diabetics?
75% of diabetics die from a cardiovascular event.
What are the three types of insulin, with examples, peak time and duration?
Ultra rapid acting - peaks @ 30-60mins, duration = 3-4 hours
Examples: Aspart, Lispro
Short acting - peaks @ 1-2 hours, duration = 6-8 hours
Examples: Regular/Neutral
Long acting - no peak (flat action), duration = 24h
Examples: Glargine, Detemir
Onset is half of minimum peak time.
Onset for long acting = 1 - 2 hours.
