Diabetes Flashcards
Define diabetes.
An inordinate and persistent increase in urinary output.
Define insipidus.
Glucose is not present in the urine.
Define mellitus.
Glucose is present in the urine.
Explain diabetes insipidus.
Copious volumes of v dilute urine (polyuria)
Polydipsia.
NO CHANGE IN URINARY GLUCOSE.
Deficient in production and release of ADH (vasopressin) from the PP. THerefore the CD is impermeable to water and there is no reasborption - all lost in the urine.
How would you treat diabetes insipidus?
Desmopression a V2 receptor agonist (analogue of ADH).
Type 1 diabetes?
Insulin independent diabetes mellitus.
10%
Low levels of absence of circulating insulin.
Type 2 diabetes?
Non-insulin dependent diabetes mellitus. 90% Reduced response to insulin. Insulin resistance. Insulin overproduced.
Symptoms of diabetes mellitus?
Elevated blood glucose >11mM (fasted conc approx 7mM) = elevated urinary glucose.
Renal transport maximum 100-175mg/min…increased urination.
Explain how untreated diabetes mellitus can cause damage to the nerve/lens
Glucose reduced to sorbital - osmotic damage
Glycosylation of alpha-crystallin - cataracts
Explain how untreated diabetes mellitus can cause damage to erythrocytes.
glycosylation of haemoglobin A1C. Oxygen then can’t be released. Normal = 5-8%. Abnormal - 12-15%.
As erythrocytes last 120 days…gives an indication how well BGL has been managed in the last few weeks.
Name 6 complications of untreated DM.
Diabetic retinopathy. Diabetic nephropathy. Diabetic neuropathy. Infection. CV disease (heart disease, peripheral vascular disease, gangrene) Diabetic coma.
Describe a diabetic coma…
HIGH BLOOD GLUCOSE…
…ketosis (increase fat metabolism, increase acetyl coA, ketones formed = metabolic acidosis, stimulates respiratory centres, deep sighing breathing).
…OSMOTIC DIURESIS
Decreased plasma volume, decrease BP, decrease GFR, increase K, increase plasma in urine.
Epidemiology of DM?
Type 1 - varies in different countries. NOT all genetically determined.
Type 2 - 85% obese, larger genetic component. Triggered by obesity?
6th leading cause of death and leading cause of blindness.
Explain how indulin is formed.
From pro-insuline. A chain and B chain linked by C peptide and attached to each other by disulphide bonds.
C peptide is cleaved.
A chain: 30aa
B chain: 21aa.
What do A cells of the pancreas secrete?
glucagon and glucagon like peptides.
What do B cells of the pancreas secrete?
insulin, c peptide and amylin
What do D cells of the pancreas secrete?
Somatostatin.
What do F cells of the pancreas secrete?
Pancreatic polypeptide.
Explain the regulation of insulin release.
1) Glucose enters beta cells via Glut-2.
2) Glucose is metabolised. Increase in ATP.
3) ATP sensitive K channels shut.
4) Cell depolarises.
5) VOCC open
6) Ca++ influx
7) Insulin containing granules are released by exocytosis.
Why is the release of insulin normally biphasic?
Rapid - release of preformed insulin,
Secondary increase - cleaved preformed precursor - slower response.
What factors stimulate insulin release?
Glucose AA FA Sympathetic B2 stimulation Parasympathetic stimulation. Oral glucose (more so than iv glucose...due to incretins...GLP-1, GIP etc).
What factors inhibit insulin release?
A2 receptors
somatostatin
high amylin concentrations.
galanin.
Describe the insulin receptor.
Tyrosine kinase receptor - dimer. Extracellular alpha subunit and intracellular beta subunit. When insulin binds…Conformational change in beta sub unit…results in autophosphorylation.
What is the action of insulin?
Increase glucose in cells by causing glut 4 (insulin sensitive) receptors to be inserted in the membrane
What effect does insulin have on CHO metabolism in adipose, liver and muscle cells?
Adipose: Stimulate glucose uptake and stimulate glycerol synthesis.
Liver: increased glycolysis, increase glycogenesis, decrease gluconeogensis and decreased glycogenolysis
Muscle: increase glucose uptake, increase glycogenesis and decrease glycogenolysis.
What effect does insulin have on fat metabolism in adipose and liver cells.
Adipose: Increase TG synthesis, decrease FA synthesis, decrease lipolysis.
Liver: increase lipogenesis and decrease lipolysis
What effect does insulin have on protein metabolism in liver and muscle cells?
Liver: decrease protein breakdown
Muscle: increase protein synthesis and increase aa uptake.
What is 1 unit of insulin.
The amount required to lower a fasted rabbits blood glucose to 2.5mM.
approx 36mg of insulin.
Describe the differences between porcine, bovine and human insulins.
Porcine - 1 aa different to human,
Bovine - 3 aa different to human,
Differences in aa between humans - determines differential duration of action.
Why do we have insulin zinc suspensions?
Insulin naturally forms crystals and zinc encourages this…longer duration and crystals don’t dissolve.
What are the main side effects of insulin preparations?
HYPOGLYCEMIA.
Neuroglycopenia - lack of glucose to brain. if severe - glucose, glucagon or adrenaline (iv)
