Week 1 Flashcards
What system consists of ductless endocrine glands that occur at numerous locations in the body?
Endocrine system
In the endocrine system - how is communication between glands and other tissues achieved?
By secretion of a hormone into blood stream and transport to a target site
Name three things that the endocrine system regulates?
- Nutrient metabolism
- H2O and electrolyte balance
- Red blood cell production
What stress hormone is long term and what is short term?
Long term - cortisol
Short term - Adrenaline
What are the three main classes of hormones?
- Glycoproteins and peptides
- Steroids - derived from cholsterol
- Tyrosine and tryptophan derivatives
Give two hormones in the protein and peptide class?
Oxytocin
Insulin
What is tyrosine enzymatically converted to?
Adrenaline
How are amines transported in plasma?
Freely - they are hydrophilic
What are peptides and proteins pre-synthesised from?
Longer precursor
With steroids - what is cholesterol converted to?
Pregnenolone - rate limiting step
How are steroids transported in the plasma?
Mainly bound to plasma proteins - hydrophobic
Are steroids and thyroxine soluble or insoluble in plasma?
Insoluble
Give two roles of carrier proteins?
- Increase amount transported in blood
2. Prevent rapid excretion by preventing filtration at kidneys
What does sex steroid-binding globulin bind to?
Testosterone and estradiol
What does albumin bind to?
Steroids and thyroxine
What does transthyretin bind to?
Thyroxine and some steroids
What helps to maintain a constant concentration of free lipophilic hormone in the blood?
Carrier proteins
Are free and bound hormones in equilibrium?
Yes`
What is the primary determinant of plasma concentration?
Rate of secretion
What does ‘tropic’ refer to?
A hormone that acts upon another endocrine gland to regulate its secretion of hormone
What secretes corticotropinreleasing hormone?
Hypothalamus
What does CTRH target which then releases Adrenocorticotropic hormone?
Anterior pituitary
What does ACTH act on which then secretes cortisol?
Adrenal cortex
Hormone receptors exist as three structurally and funtionally distinct types - name the two cell surface receptors and the one intracellualr receptor?
GPCR
Receptor kinases
nuclear receptors
What are class 1 nuclear receptors activated by?
Steroid hormones
What are class 2 nuclear receptors activated by?
Lipids
What are hybrid class nuclear receptors activated by?
Thyroid hormone
What type of receptor is this: binding of insulin causes autophosphorylation of intracellular tyrosine residues. recruitment of multiple adapter proteins, notibly IRS1, that are also tyrosine phosphorylated?
Receptor kinases
What are nuclear receptors?
Ligand-gated transcription factors
What four cells are in pancreatic islets - in order of most abundant first?
- Beta-cells
- Alpha-cells
- Gamma-cells
- PP cells
What do beta-cells secrete?
Insulin
What do alpha cells secrete?
Glucagon
What do gamma cells secrete?
Somatostatin
What do PP cells secrete?
Pancreatic polypeptide
What is synthesised in the rough ER of pancreatic beta-cells as a larger single chain preprohormone - preprosinsulin?
Insulin peptide
During secretion of insulin: how does glucose enter beta-cells and what phosphorylates it>
GLUT2 glucose transporter
Glucokinase
What phosphorylates glucose at very low concentrations?
Hexokinase
What does an increased metabolism of glucose lead to in relation to intracellular ATP concentration>
An increase
In relation to insulin secretion: what does ATP inhibit?
ATP-sensitive K+ channel Katp
During insulin secretion: what depolarises the cell membrane?
Inhibition of Katp
During insulin secretion: what does depolarisation of cell membrane result in?
Opening of voltage-gated Calcium channels
During insulin secretion: what does an increase in internal calcium concentration lead to?
Fusion of secretory vesicles with the cell membrane and release of insulin
How is the release of insulin described?
Biphasic
Name the two Katp channel proteins?
Kir6.1 - inward rectifier subunit, pore subunit
SUR1 - sulphonylurea receptor, regulatory subunit
What structure are Katp channels?
Octomeric
What class of drugs directly inhibits Katp?
Sulphonylurea - tolbutamide or glibenclamide
What drug stimulates Katp?
Diazoxide - which inhibits insulin secretion
What do HNF transcription factors play a key role in?
Pancreas foetal development and neogenesis and regulate beta cell differentiation and function
When can sulphonylurea be used instead of insulin?
When there has been robust genetic screening to differentiate MODY from type I diabetes
What type of diabetes involves a loss of insulin secreting beta cells?
Type I
What type of diabetes involves defective glucose sensing in the pancreas and/or loss of insulin secretion?
MODY
What type of diabetes is initially hyperglycemoa with hyperinsulinemia so the primary problem is reduced insulin sensitivity in tissues?
Type II diabetes
What family of receptors does insulin receptor belong to?
Receptor tyrosine kinases
Is protein phosphorylation reversible?
Yes
What do protein kinases promote?
Protein phosphorylation
Name the three amino acids that protein phosphorylation occurs on? (any hydroxyl group)
Serine
Threonine
Tyrosine
What is introduced onto proteins when they get phosphorylated~?
A large negative charge
Name a dimeric tyrosine kinase?
Insulin receptor
What is insulin receptor composed of?
2 Extracellular alpha subunits and two transmembrane beta subunits linked by disulfide bonds
What binds to alpha subunit in insulin receptor?
Hormone-binding (insulin) domains
What binds to beta subunits in the insulin receptor?
ATP-binding and tyrosine kinase domains
How does the insulin receptor work?
Binding of insulin to alpha subunits causes beta subunits to phosphorylate themselves, thus activating the catalytic activity of the receptor
What two pathways does IRS activate once the insulin receptor substrates are phosphorylated?
- Ras/MAP kinase pathway and gene expression
2. PI3K, PKB, and glycogen synthesis
During insulin signalling simplified - what does PKB stimulate?
GLUT 4
What three things does the biological effect of insulin stimulate?
- DNA synthesis
- Protein synthesis
- Glycogen synthesis in liver and muscle
What two things does the biological effect of insulin uptake?
- Amino acid uptake in muscle
2. Glucose uptake in muscle and adipose tissue
What are lipolysis and gluconeogenesis in the liver a biological effect of?
Insulin
Severe insulin resistance and diabetes can be due to a mutation in what?
AKT2
What disease is a rare autosomal recessive genetic trait, involves mutations in the gene for the insulin receptor, severe insulin resistance and is caused by defects in insulin binding orr insulin receptor signalling?
Leprechaunism or Donohue syndrome
Give three developmental abnormalities of leprechaunism or donohue syndrome?
- Elfin facial appearance
- Growth retardation
- Absence of subcutaneous fat, decreased muscle mass
What is the rare autosomal recessive genetic trait that involves severe insulin resistance, hyperglycemia and compensatory hyperinsulinemia, developmental abnormalities and acanthosis nigricans?
Rabson Mendenhall syndrome
Where are ketone bodies formed?
In liver mitochondria - derived from acetyl-CoA fro, beta-oxidation
What does ketone body formation depend on?
Oxaloacetate
What is oxaloacetate consumed for?
Gluconeogenesis
What type of diabetes is ketoacidosis most associated with?
Type I