Introduction to Diabetes mellitus (16) Flashcards
What is GLUT-4?
- glucose transporter
- found in myocytes and adipocytes
- highly insulin- responsive
- lies in vesicles within cells
- when blood glucose inc., insulin released–> recruits vesicles–> placed in cell membranes
- hydrophobic outside, hydrophilic inside
What are the effects of insulin on myocytes?
- insulin inhibits breakdown of protein (proteolysis)
- reduces oxidation of AAs
- stimulates protein synthesis (along with IGF-1 and GH)
What are the effects of glucagon and insulin in hepatocytes?
- glucagon helps uptake of AAs into liver–> in fed state (lots of glucose), insulin inc. protein synthesis from AAs
- insulin inhibits gluconeogenesis in fed state
- during fasting, glucagon and cortisol inc. gluconeogenesis–> inc. hepatic glucose output (HGO)
What is lipoprotein lipase?
LPL- enzyme that breaks down triglycerides (too big to otherwise enter adipocytes)
N.B. this process is activated by influx of insulin
What are the effects of insulin and other various hormones in adipocytes?
- triglycerides w/ help of LPL and insulin broken into glycerol and NEFA–> taken up by adipocyte
- in fed state, glucose also taken up–> inc. by insulin
- in fed state, insulin converts glycerol and NEFA to triglycerides for storage and inhibits breakdown of triglycerides/glycolysis (encouraged by GH and cortisol in fasting state)
What is special in terms of cerebral energy requirement?
cannot use fatty acids for energy, only glucose (preferred) and ketone bodies
What is the effect of insulin on fatty acyl-coA in the liver during the fed state?
inhibits the breakdown of fatty acyl-coA to ketone bodies
What is the effect of glucagon on fatty acyl-coA in the liver during the fasting state?
stimulates breakdown of fatty acyl-coA to ketone bodies
What is hepatic glycogenolysis?
generation of glucose from stored glycogen in the liver- stimulated by glucagon
What is the difference between glycogen in the liver and in the muscle?
glycogen in liver can be converted to glucose and be released, whereas muscle can’t release glucose, so can only be used internally
What are the effects of glucagon and GH in the fasting state on the myocytes?
inhibition of glucose uptake
What happens overall in the fasting state?
- low insulin:glucagon ratio
- inc. NEFA
- dec. AAs when prolonged bc used up
- inc. proteolysis
- inc. lipolysis
- inc. HGO from glycogen and gluconeogenesis
- muscle can use lipids
- brain uses glucose, and later use ketones
- inc. ketogenesis when prolonged fast
What happens overall in the fed state?
- stored insulin released (1st) then slower 2nd phase release
- high insulin:glucagon ratio
- stops HGO
- inc. glycogen
- dec. gluconeogenesis
- inc. protein synthesis
- dec. proteolysis (bc lots of glucose available for energy)
- inc. lipogenesis (storing fats, bc not needed as energy source)
What tests can be done for diagnosis of Diabetes Mellitus?
2 positive tests OR 1 positive test + osmotic symptoms (thirst, urine, weight):
- fasting glucose >7.0 mmol/L
- random glucose >11.1 mmol/L
- oral glucose tolerance test (fasting glucose, 75g glucose load, 2h glucose)
- HbA1c >48 mmol/mol
What is the pathophysiology of type 1 diabetes?
- autoimmune: beta cells attacked by body- cannot secrete insulin
- absolute insulin deficiency
- inc. HGO, proteolysis and lipolysis (if prolonged–> produces ketone bodies)
- diabetic ketacidosis- serious acute complication
How does T1DM present?
- weight loss bc proteolysis- lose muscle mass
- hyperglycaemia
- glycosuria (glucose in urine) w/ osmotic diuresis
- ketones in blood and urine
What are useful diagnostic tests for T1DM?
- GAD and IA2 antibodies
- C-peptide (low bc not producing insulin)
- presence of ketones
What happens during insulin induced hypoglycaemia in T1DM?
too much insulin injected:
- switches off hepatic gluconeogenesis (no glucose made in liver)
- more and more glucose taken up by muscle cells
N.B. counter regulatory responses e.g. inc. glucagon are not enough to stop hypoglycaemic episode
What is meant by impaired awareness of hypoglycaemia?
- reduced ability to recognise symptoms of hypoglycaemia (body lowers its threshold at which you start to feel symptoms and act)
- counterregulatory response kicks in at a lower level
- recurrent hypoglycaemia
What are the autonomic symptoms and signs of hypoglycaemia?
- sweating
- pallor
- palpitations
- shaking
What are the neuroglycopenic symptoms and signs of hypoglycaemia?
- slurred speech
- poor vision
- confusion
- seizures
- loss of consciousness
How do we define a severe hypoglycaemic episode?
where a person needs third party assistance to treat the episode
Where does insulin resistance reside in T2DM?
liver, muscle, and adipose tissue
What are the clinical manifestations of insulin resistance?
- high triglycerides
- low HDL
- hypertension (high bp)
- high waist circumference (fat storage)
- high fasting glucose
