Introduction to diabetes mellitus Flashcards
Metabolic actions of insulin relating to glucose
Decrease hepatic glucose output (HGO)
Increase glucose uptake in muscle
Metabolic actions of insulin relating to proteins
Decrease proteolysis
Metabolic actions of insulin relating to lipids
Decrease lipolysis
Decrease ketogenesis
What does insulin have mitogenic actions on?
Lipoproteins Smooth muscle hypertrophy Ovarian function Clotting Energy expenditure
How does insulin drive glucose into muscle?
Via GLUT-4
Where is GLUT-4 stored?
In vesicles
What does insulin cause for GLUT-4?
GLUT-4 incorporated into the membrane on muscle cells
Hydrophilic core allows glucose transport
Hydrophobic exterior means it can sit in membrane
How does glucose uptake change when insulin is released?
Insulin causes a 7-fold increase in glucose uptake
How does insulin affect the use of protein in muscle cells?
Increase protein synthesis
Decrease proteolysis
Glucose in blood
Present all the time
Not only after meals
What is the name of stored glucose in the liver?
Glycogen
In the liver, when blood glucose is low, (fasting state) gluconeogenesis occurs
Break down protein
Gluconeogenic AAs can be used to make glucose
In the liver, when blood glucose is high and insulin is released
Gluconeogenic AAs can enter liver and be used to make protein
Carbohydrate in the form of glycogen in liver and muscle is a
short term energy store
Fat has a high energy concentration
Takes a long time to break down
Insulins’ effect on adipocytes
In blood, Triglyceride broken down by lipoprotein lipase (encouraged by insulin), so
Glycerol and NEFAs can enter adipocyte.
Glucose can enter via GLUT-4 and can be used to make NEFAs and glycerol-3-P.
Insulin within cell encourages formation off triglyceride
Triglyceride can be broken down in fight or flight
To make glycerol and NEFA
NEFA
Non-esterified fatty acid
How do we store fat?
In adipocytes
Omental adipocytes
more metabolically and endocrinology active due to anatomical location (Central)
What does more omental fat increase?
Risk of heart disease
Glycerol enters liver cells
Phosphorylated to make Triacylglyerol (Triglyceride)
Triglyceride can be used to make glycerol and then glucose
= Gluconeogenesis
NEFA in liver cells
Can’t be used to make glucose, only the glycerol bit
What can the brain use as energy substrates?
Glucose
Ketone bodies
What can’t the brain use as an energy substrate?
Fatty acids
Brain fundamentally different from other parts of body
Fatty acids can be used to make ketone bodies
Insulin stops this
Glucagon stimulates this
How can NEFAs be used to make ketone bodies?
NEFA enter liver
NEFA broken into Acetoacetate and 3-Hydroxybutarate
Which leave liver as ketone bodies
What does the conversion of NEFAs to ketone bodies allow?
Brain function after fasting
If someone has ketones present and a high blood glucose
They are insulin deficient
As when there is plenty of glucose, it is unnecessary to make ketone bodies
What can glycogen in liver be broken down into?
Glucose by glucagon
= glycogenolysis
2 ways of supporting HGO
Glycogenolysis
Gluconeogenesis
Why can’t muscle release glucose?
Glycogen in muscle is just used by muscle, can’t be used to support plasma glucose
Fasted state concentrations
Low insulin to glucagon ratio
Glucose conc. 3-5.5 mol/l
Increase conc. NEFA
Decrease conc. AA
Fasted state actions
Increase proteolysis, lipolysis, glycogenolysis and gluconeogenesis
Increase HGO
Fasted state use of energy substrates
Muscle uses lipids
Brain uses glucose, later ketones
Increased ketogenesis in brain when prolonged fasting
Fed state concentrations
Stored insulin released, then 2nd phase
High insulin to glucagon ratio
Increase conc. glycogen
Fed state actions
Increase protein synthesis and lipogenesis
Decrease proteolysis and gluconeogenesis
Presentation of T1DM
Absolute insulin deficiency
How does weight loss occur in T1DM?
Proteolysis and lipolysis continue
T1DM Glucose exceeds kidneys ability to reabsorb glucose
= Glucose and ketones in urine
Glycosuria and ketonuria with osmotic symptoms
Insulin induced hypoglycaemia
Increased insulin so Glucose enters muscle
Glucagon increases, triumphs over insulin
Increase HGO with gluconeogenesis and glycogenolysis
Increase in catecholamines, cortisol and growth hormone
How to treat insulin induced hypoglycaemia in an emergency
Intravenous/ intramuscular glucagon
T2DM insulin resistance resides in
Liver, muscle and adipose tissue
Affects intermediary metabolism, glucose and fatty acids
In T2DM insulin resistance, there is usually enough insulin to suppress
Ketogenesis
Proteolysis
So don’t lose weight or produce unnecessary ketones
What are the 2 effects insulin has after binding to the insulin receptor?
MAP Kinase pathway
Insulin receptor PI3 Kinase pathway
What is the Insulin receptor PI3 Kinase pathway?
Metabolic actions on glucose, fats and AAs
What is the MAP kinase pathway?
Causes growth and proliferation
Which pathway is affected in T2DM insulin resistance?
Insulin resistance PI3 Kinase pathway
Compensatory hyperinsulinemia
Functional pancreas but
resistance in the PI3 kinase pathway leads to excessive insulin production to reduce blood sugar
Thus increasing MAP kinase pathway - overstimulating growth (mitogenic) pathway
What does compensatory hyperinsulinemia cause?
Patient does NOT have T2DM
May have high BP, risk of ischaemic heart disease
Hyperinsulinaemic effect of mitogenic effects in insulin resistance
Low HDL cholesterol
Smooth muscle hypertrophy
Reduced ovarian function
Abnormal effects on clotting and energy expenditure
Metabolic effect in insulin resistance
Insulin resistance effect Fasting glucose >6mmol High [TG] Low [HDL] High BP High waist circumference
BP is a major issue in T2DM
Causes damage to arteries
Presentation of T2DM
Insulin resistance Majority obese Dyslipidaemia Later insulin deficiency Hyperglycaemia Less osmotic symptoms With complications
Dyslipidaemia
Abnormal carriage of lipids in circulation
Why is T2DM often presented with complications?
Often not found for years
Subtle
Healthy eating for T2DM
Total calorie control
Reduce calories from fat and refined carbohydrate
Increase soluble fibre and calories from complex carbohydrate
Decrease sodium
