insulin action Flashcards
describe insulin metabolic action
decrease HGO increase muscle uptake of glucose decrease proteolysis decrease lipolysis decrease ketogenesis
list the mitogenic actions of insulin in insulin resistance
affects on: lipoproteins smooth muscle hypertrophy - important in high Bp ovarian function clotting energy expenditure
describe glucose transporter 4
GLUT 4 hydrophilic core hydrophobic outside in muscle and adipose tissue insulin responsive lies in vesicles recruited to membrane and enhanced by insulin 7 fold increase in glucose uptake pre-made - allow glucose through membrane
describe action of insulin on muscle
stimulates protein synthesis
inhibits proteolysis and O2-CO2
what can AA in the circulation do
go to liver and used to make glucose - gluconeogenic eg alanine
describe glucose and glycogen
glucose in blood all time at low and regulated concentration
glycogen - short time store in liver
After fasting what happens in the liver
glucagon enters proteolysis -- aa -- glucose maintain HGO inhibited by glucose gluconeogenesis - gluconeogenic AA - pyruvate and lactate
what stimulates gluconeogenesis
Glyg
cats
Cort
how long are each of the fuel stores present
glycogen 16hours
protein 15days
fat 30-40days
describe the action of insulin after a meal
insulin stimulate break down of triglyceride by lipoprotein lipase in the blood vessel
nonesterified fatty acid and glycerol enter adipocyte
glucose enter through glut 4 -break into 2C segments - NEFA and glycerol enters normally and some is made from glucose
insulin then encourages the formation of triglycerides in the adipose cell
which hormones stimulate break down of triglycerides in fight/flight
catecholamines
cortisol
GH
describe the circulation in the blood
circles through omental circulation to gut and liver to pick up nutrients before entering systemic circulation.
adipocytes different in central circulation to in arms and legs - able to change met more, met and endo more active - predict ischemic heart disease - large stomach
describe hepatic gluconeogenesis
glycerol enter liver
phosphorylated – glycerol 3p – glucose
maintain HGO
glycerol 3 p can also make TG
NEFA enter TCA so can’t be used to make glucose `
what source of energy can the brain use
glucose and ketone bodies
what happens when NFEA enters body after fasting
shuttle on mt membrane – fatty acyl CoA make ketone bodies: acetoacetate and acetone + 3 OH-B
leave liver
sign of insulin deficiency because insulin stop ketone body production
if ketone bodies present with glucose - no insulin (T1DM)
describe hepatic glycogenolysis
glucose enter liver - phosphorylated glucose-6-p
insulin encourage to glycogen
Cats and glucagon encourage glycogenolysis forming glucose-6-p – glucose – increase HGO
what happens when glucose enters the muscle
enter through glut 4
inhibited by GH, cats and cort
stored as glycogen
muscle can’t release glucose - stay in muscle and enter TCA for energy in muscle
what happens in the fasted state
increased: proteolysis, lipolysis, HGO from glycogen and gluconeogenesis (from glycerol and AA - continually release glucose), muscle use lipids, brain use glucose then ketones, ketogenesis when prolonged, [NEFA]
low insulin to glucagon ratio, [glucose]=3-5.5mmol/l
decreased [AA] when prolonged
what happens in the fed state
stop HGO (no need)
increase glycogen store, protein synth, lipogenesis
decrease the opposites
stored insulin release then 2nd phase high [insulin] to [glucagon] ratio
link obesity to T2DM
insulin injections don’t work
obesity - 1 of many factors but not necessarily the cause of diabetes
what is the presentation of T1DM
absolute insulin deficiency high HGO glucose and ketones in urine loss of muscle - proteolysis and fat hyperglycaemia glycosuria with osmotic symptoms ketouria
describe insulin induced hypoglycaemia
glucose enters muscle
eventually glucagon, cat, cort and GH increase HGO - imporove without intervention but may have accident in time
family can give intramuscular glucagon - better before paramedics turn up
describe insulin resistance
affects intermediary metabolism
reside in muscle, liver and adipose - all 3
enough insulin to suppress ketogenesis and proteolysis - don’t lose weight and no inappropriate ketone production
Insulin receptor and mitogenic
Insulin receptor MAPK pathway - growth and proliferation in utero and Children
high Bp and dyslipidaemia in adults
Insulin receptor metabolic actions
IRS - insulin receptor substrates
PI3K-Akt pathway
Insulin resistance resides in this pathway
metabolic actions on glucose fat and AA
Functioning pancreas - insulin conc increases, glucose normal - don’t have diabetes - stimulate mitogenic pathway so people have High Bp and Abnormal lipid carriage lead to ischaemic heart disease
some therapeutic medications
describe insulin action in insulin resistance
glucose protein and lipid normal
hyperinsulinaemic effect on mitogenic growth - excess stimulation of lipoproteins (less HDL - good cholesterol) abnormal lipoproteins - damage of arteries , smooth muscle hypertrophy - high Bp, ovarian function - polycystic ovarian syndrome, clotting, energy expenditure
2 major contributors to ischaemic heart disease - hypertension and lipoproteins
what does insulin resistance cause - intermediary metabolism
high TG
low HDL
high fasting glucose >6mmol/l
high waist circumference
hypertension Bp >135/80
adipocytokines, inflammatory state, energy expenditure - used as a therapeutic target
might not have all of these in a person with diabetes
presentation of T2DM
insulin resistance
60-80% people obese at presentation - central adiposity
dyslipidaemia - abnormal carriage of lipid in circulation, more subtle feature of IR at presentation
later insulin deficiency
hyperglycaemia
less osmotic symptoms
with complications
management of DM
control: total calories, calories as fat, refined carb (more for T1 - match to insulin), increase calories as complex carbs - longer to absorb, increase soluble fibre, decrease sodium
