Endocrinology - introduction to diabetes mellitus Flashcards
In what tissues is GLUT4 common?
Muscles and fat
(myocytes and adipocytes)
What are characteristics of GLUT4 receptor?
insulin depdenet
7-fold increase glucose uptake
lies in vesicles
Effect of insulin on muscle cell?
increase GUT4 expression on CM
increased protien synthesis (helped by other hormones)
What effect can cortisol have on muscle cells?
proteolysis
and transportation glucogenic amino acids in blood to liver
(as starving state so low glucose so body uses alternative energy sources)
what effect does insulin have on liver (glucogenesis)?
What are 3 fuel sources of body? How long does each last?
short term - carbs stored in liver and muscles i.e glucagon
What is lipoprotein lipase function (enzyme)?
breaks down trigglycerides in blood so able to leave circulation (it’s too big)
moves into adipose tissue
breaks it down into glycine and non esteric fatty acids
What happens to glycerol and NEFA in adipose tissue?
If insulin present converted to trigylceride (stored) + stimulated uptake of glucose via GLUT4
When cortisol/GH present break down triglycerides that are stored to glycerol and NEFA that are released into blood to liver
What is the hepatic portal circulation?
What is it’s function?
takes nutrients straight to liver for processing
and insulin release quickly to rest of body
What happens to glycerol released into blood?
Take into liver + fed stored at triglycerides
when fasting glucogensis to produce glucose
What is unique about brains usage of fuels?
doesn’t use fatty acid
MOST preferred glucose
if needed use ketone bodies
How are ketone bodies produced in fasting state?
NEFA (from breakdown of triglyercides in adipose tissue) coverted to ketone bodies in liver
ketone bodies another alternative body fuel
problem: WHEN both GLUCOSE and KETONE BODIES in blood
What hepatic glycogenolysis?
when fed state GLU4 uptake of glucose stored as glycogen
Where else in the body is glycogen stored?
muscles
released back to glucose when needed i.e fasting
Can also use NEFA as energy source
NOT able to release glucose into circulation
overall what happens in fasted state?
low insulin
high glucagon
normal/lower side glucose
high NEFA levels
up intially but used up so after a while low amino acid levels
breakdown protiens and lipids
increase hepatic glucose
muscle use lipids as energy source
brain use glucose then ketone bodies
if prolonged ketone production
What are diagnosis of diabetes mellitus
Fasting glucose > 7.0mmol/L
Random glucose >11.1mmol/L
Oral Glucose Tolerance Test
Fasting glucose
75g glucose load
2-hour glucose
HbA1c >48mmol/mol
Diagnosis requires 2 positive tests or 1 positive + osmotic symptoms
What physiology of Type 1 diabities (genetic)?
autoimmune - death B cells
no insulin produced
How does it affect metabolism?
a lot of urine produced. As a lot of glucose in urine, osmotic diarhosis.
production a lot ketone bodies (ketoacidosis)
Symptoms of T1 diabities?
weigh loss
hypergycaemia
glycosuria- polyuria, nocturia, polydipsia
ketones in blood and urine
Diagnosis test for T1 diabities rather than T2?
Antibodies - GAD, IA2
C-peptide - low c peptide
presence of Ketones
What are complications insulin?
Can cause hypoglycaemia which is has horrible side effects
Body’s reponse to hypoglycaemia?
Increase cortisol, GH, glucagon, catecholamines that have a ‘fed state’ respsonse
incarease lipolysis
increase hepatic glucose
increase glucogenolysis
increase gluconeogenesis
effect on awarness of hypoglycaemia?
reduced ability reconginse HYPO
due to loss of counterreg reponse - as body so use to having it
reccurent HYPO - body use to having this exprience, higher thershold
Symptoms of hypoglycaemia
autonomic - sweating, pallor, palpatations, shaking
neuroglycopenic - slurred speech, poor vision, confusion , seizures, loss of consciousness
severe - need 3rd party assistance
pathophysiology of T2 diabities?
insulin resistance residues in liver, muscle and adipose tissues
effects metabolism of glucose, fatty acid
enough insulin prevent ketogenesis and proteolysis
What is insulin resistance mechanism?
When binds activates P13K - Akt (metabolism) and MARK pathway ( growth)
effects on P13K - Akt pathway but body produced more insulin for effect
MORE STIMULATION FOR metabolic actions
effects of insulin resistance
hypertension
increased weight
high glucoses
low LDL, high TG
inflammatory resp
adipocytokines
decrease energy expenditure
symptoms of T2 diabites
hyperglycaemia
overweight
dyslipidaemia
less osmotic symptoms - urine
later inulsin deficnicu
eye disease
renal failure
nerve disease
stroke
Dietary reccomend and education?
total calories
reduce fat
reduce refined carbs
increase complex carb
decrease sodium
increase soluble fibre
DAFNE - type 1
DESMON - type 2
mangement of diabites mellitus?
