Biochemistry Flashcards
What are the functions of alpha, beta and delta cells in the pancreas?
Alpha - secretes glucagon
Beta - secretes insulin
Delta - secrete somatostatin
What is the structure of proinsulin?
2 polypeptide chains linked by disulphide bonds
A connecting C peptide
How is pro-insulin turned into insulin?
The C peptide is cleaved
What type of synthetic insulin is lispro?
Ultra fast-acting
How is ultra fast-acting insulin used?
Injected within 15 minutes of beginning a meal
Used in combination with a longer-acting preparation for T1DM unless used for continuous infusion
What type of synthetic insulin is glargine?
Ultra long-acting
How is ultra long-acting insulin used?
Administered as a single bedtime dose
What are the steps of insulin secretion by beta cells?
- Glucose uptake through GLUT2 transporter
- Glucokinase phosphorylates glucose to glucose-6-phosphate
- Phosphorylated glucose-6-phosphate enters the glycolysis pathway and undergoes oxidative phosphorylation to generate ATP
- Increased intracellular ATP inhibits the KATP channel - depolarisation
- Depolarisation causes opening of voltage gated calcium channels
Influx of calcium causes insulin secretion
At what glucose concentration do normally-functioning beta cells release insulin?
5mM
How many phases is insulin release in?
2
Which phase of insulin secretion is larger?
Phase 1
Why are there 2 phases of insulin secretion?
There are 2 pools of insulin granules
The readily released pool are immediately available for release and prevent a sharp increase in blood glucose
The reserve pool has to undergo preparatory reactions to become available for release - after this the second phase is more tuned to the glucose intake
How does the pattern of release of insulin secretion change in T2DM?
Not biphasic - a weaker and flatter response
What is type 1 diabetes?
Autoimmune destruction of pancreatic beta cells, making them incapable of secreting insulin
What is type 2 diabetes?
Reduced insulin sensitivity in tissues and later a decline in beta cell function
What is Maturity Onset Diabetes of the Young?
Defective glucose sensing in the pancreas and/or loss of insulin secretion
What is neonatal diabetes?
Mutations causing dysfunction of the glucose sensing mechanism
What is gestational diabetes?
When beta cell function decreases in pregnancy
What are the biological effects of insulin?
Amino acid uptake in muscle DNA synthesis Protein synthesis Growth responses Glucose uptake in muscle and adipose tissue Lipogenesis in adipose tissue and liver Glycogen synthesis in liver and muscle Inhibits lipogenesis and gluconeogenesis in the liver
What is insulin resistance?
The reduced ability of cells to respond to ‘physiological’ insulin levels
What are the rare genetic causes of diabetes?
Leprechaunism (Donohue syndrome)
Rabson Mendenhall syndrome
What is diabetes ketoacidosis?
A build up of ketone bodies
What are ketone bodies?
Molecules that form in the liver mitochondria derived from acetyl-CoA from beta oxidation
How can diabetes lead to diabetes ketoacidosis?
Usually insulin inhibits lipolysis and therefore reduces risk of ketone body overload
If insulin supplementation is missed and hyperglycaemia ensues ketone bodies can build up
What are the symptoms of diabetic ketoacidosis?
Vomiting
Dehydration
Increased heart rate
Smell of acetone on breath
How is diabetic ketoacidosis diagnosed?
High ketones and glucose
Low or absent insulin
Low pH
How is diabetic ketoacidosis treated?
Insulin and rehydration
What are the different hormone subtypes?
Proteins and peptides
Amino acid derived
Steroid hormones
What are the different hormone receptor types?
G protein coupled receptors
Receptor tyrosine kinase families
Receptors associated with tyrosine kinase activity
Steroid hormone receptor
How do G protein coupled receptors work?
Ligands bind on extracellular membrane
Signalling pathway activated intracellularly
How do receptor tyrosine kinase receptors work?
Binding occurs extracellularly, causing an intracellular effect
What is an example of a tyrosine kinase receptor?
Insulin receptor
What are examples of cytokine receptors?
Prolactin receptor
Growth hormone receptor
How do steroid hormone receptors work?
Binding occurs instracellularly in the cytoplasm or nucleus
Results in changes in gene transcription
What is an example of a steroid hormone receptor?
Glucocorticoid receptor
What is the hypothalamic-pituitary axis?
The hypothalamus stimulates the pituitary gland to release hormones
Release of these hormones inhibit the hypothalamus and stop it stimulating the pituitary gland
By what mechanism does the hypothalamic-pituitary axis work?
Negative feedback
What is the thyroid axis?
The hypothalamus stimulates the pituitary gland which releases thyroid-stimulating hormone (TSH) which stimulates the thyroid gland to secrete thyroid hormones
The thyroid hormones, and TSH inhibit the hypothalamus and the pituitary gland
What does the level of TSH indicate about the function of the thyroid gland?
Raised TSH - hypothyroidism
Suppressed TSH - hyperthyroidism
