cell communication 1 Flashcards
role of glucocorticoid class steroid hormone
glucocorticoid class steroid hormone
• released in response to stress and reduced blood sugar levels
• key part of our bodies response to stress
• also affects metabolism, immune system, electrolyte balance and memory
Addisons Disease symptoms and pathology
Addisons Disease
• primary adrenal insufficiency: damage to the adrenal glands
• secondary adrenal insufficiency: lack of ACTH
• depression, flu-like symptoms, nausea, weight loss
• Addisonian crisis - caused by sudden severe stress eg. accident, operation, infection
Cushings syndromes symptoms and pathology
increased levels of cortisol Cortisol
can be caused by a benign
adenoma growing in the pituitary gland leading to increased ACTH production
• also caused by long term steroid use / abuse
• weight gain, raised blood pressure, puffy face, hair growth
type 1 diabetes pathology
Type 1 diabetes : destruction of β cells - often as a result of auto-immune attack
insulin molecule shape and structure
Consisting of two α subunits and two β subunits, insulin receptor is a heterotetramer with subunits linked through disulfide bonds to form columnar structures
effects of insulin ligand binding to receptor
ligand binding triggers a conformational change
moves two kinase domains closer together
kinase domains trans-phosphorylate
in addition, a closely associated docking protein insulin receptor substrate 1 (ISR1) also becomes tyrosine phosphorylated
Following insulin binding what are the steps of the different substrates that are then activated/ phosphorylated
Following insulin binding, the insulin receptor (IR) tyrosine kinase is activated,
causing tyrosine phosphorylation of IR and of the IR substrate (IRS) proteins.
p-Tyrosine sites on IRS allow binding of the lipid kinase PI3K, which synthesizes PIP3 at the plasma membrane
PIP3 recruits the phosphoinositide-dependent kinase (PDK), which directly phosphorylates the Thr308 residue of AKT
Activated AKT goes on to phosphorylate a number of substrates at Ser/Thr residues.
These include: The forkhead family box O (FOXO) transcription factors
The protein tuberous sclerosis 2 (TSC2)
The three major biochemical
steps in insulin signalling are:
The three major biochemical
steps in insulin signalling are:
1) tyrosine phosphorylation of the receptor and its direct substrates (IRS)
2) activation of the lipid kinase, PI3K
3) activation of multiple serine/ threonine kinases, the most important of which is AKT.
Good control of glucose levels depends on two ‘types’ of insulin
long acting ‘background’ insulin replacement fast acting ‘bolus’ with meals to deal with
what can excess insulin cause –
Excess insulin can ultimately lead to hypo-glycemia (hypo)
liver & muscles being stimulated to take up glucose too little blood sugar
brain can ONLY metabolise glucose
can ultimately lead to unconsciousness and death
Type 2 diabetes mellitus (T2DM) pathology and symptoms
Type 2 diabetes mellitus (T2DM)
- dysregulation of carbohydrate, lipid and protein metabolism
- impaired insulin secretion, insulin resistance or a combination of both.
feeling very thirsty passing urine more often than usual, particularly at night feeling very tired weight loss and loss of muscle bulk slow to heal cuts or ulcers frequent vaginal or penile thrush blurred vision
what is metformin
Metformin is an antihyperglycemic agent of the biguanide class, used for the management of type II diabetes
Metformin is an insulin sensitizer leading to a decrease in insulin resistance and a clinically significant reduction of plasma fasting insulin levels.
how does metformin work
As this drug is positively charged, it accumulates in cells and in the mitochondria because of the membrane potentials across the plasma membrane as well as the mitochondrial inner membrane.
Metformin inhibits mitochondrial complex I, preventing the production of mitochondrial ATP leading to increased cytoplasmic ADP:ATP and AMP:ATP ratios
These changes activate AMP-activated protein kinase (AMPK), an enzyme that plays an important role in the regulation of glucose metabolism
