Introduction to Diabetes Mellitus: Insulin action (5) Flashcards
What effect does insulin have on glucose
it decreases hepatic glucose output and increases uptake of glucose by muscles
What effect does insulin have on protein
it decreases proteolysis (breakdown of protein)
What effect does insulin have on lipids
it decreases lipolysis and decreases ketogenesis
What other effects does insulin have
growth, vascular effects, ovarian function, clotting and energy expenditure
what transporter is glucose uptake through
Glucose Transporter 4 (GLUT 4)
Where is GLUT 4 particularly abundant
in muscle and adipose tissue
What stimulates GLUT 4
insulin
Describe the structure and location of GLUT 4 in cells
It has hydrophobic elements on the outside embedded in the membrane and a hydrophilic core which allows glucose into the cell. GLUT-4 sits in vesicles within the cytoplasm
How does insulin cause a 7 fold increase in glucose uptake
insulin recruits GLUT 4 to the membrane. they are insulin responsive
What does cortisol do in muscle cells when we are stressed
increase proteolysis
what effect does insulin have on amino acids in muscle cells
prevents the oxidation of them and increases the re-synthesis of proteins from amino acid
what are gluconeogenic amino acids
amino acids that have entered the circulation and moved to the liver where they are used to produce glucose
how do gluconeogenic amino acids enter the liver
via specific transporter channels.
what increases the uptake of amino acids into the liver
glucagon
what does insulin stimulate in the liver
protein synthesis
What increases gluconeogenesis in the liver
Somatotrophin, Cortisol, Catecholamines and Glucagon
What inhibits gluconeogenesis in the liver
insulin
what is hepatic glucose output (HGO)
glucose produced by gluconeogenesis in the liver that enters the circulation
What are triglycerides broken down by before they can enter the adipocyte
lipoprotein lipase stimualated by insulin
what is the triglyceride broken down into
glycerol and non esterified fatty acids
why does glucose enter the adipocyte
to be used to make NEFA with glycerol and non esterified fatty acids
how can glucose be used to make triglycerides
it can be chopped up to make 2 glycerols and the fatty acids can be stuck to the glycerol to make triglycerides
what effect does insulin have on fat in the blood
breaks down fats so it can enter the adipocyte
what effects does insulin have on fat in the adipocyte
promotes formation on triglyceride and storage of fat and inhibits lipolysis
why is waist circumference a simple indicator of an individuals risk of ischaemic heart disease
blood reaches the gut and there is a portal system connecting the intestines to the liver. the blood passes through the liver for the absorbed food to be processed. adipocutes in the gut are different in activity and endocrine regulation compared to the rest of the body
what is glycerol from adipocytes and food entering the liver used for
to make triglycerides which then enter lipoprotein particles
what can glycerol also be used to make
glucose and this supports hepatic glucose ouput
why cant fat do even though glycerol can be used to make glucose
reenter the glucose pathway
what happens after a 10 hour fast
25% of our hepatic glucose output is supported by new glucose production
what fuel can the brain use and not use
can use glucose and ketone bodies but cannot use fatty acids
what can fatty acids made from lipolysis be used to make in the liver
ketone bodies
what is the effect of insulin on ketone body synthesis in the liver
it inhibits the conversion of Fatty Acyl CoA to ketone bodies
high blood glucose + high ketone bodies =
insulin deficient
definition of ketones
three water soluble molecules that are produced by the liver from fatty acids during periods of low food intake or carbohydrate restriction.
what are the three ketone molecules
acetone, acetoacetic acid, beta-hydroxybutyric acid
what promotes hepatic glycogenesis
insulin, glucagon and catecholamines
what is glucose converted to in the liver
glucose-6-phosphate
what are the 2 processes that support hepatic glucose output
gluconeogenesis and glycogenolysis
what promotes uptake of glucose by GLUT-4
insulin
what inhibits uptake of glucose by GLUT-4
stress hormones - GH, CATS, CORT
what is glucose stored as in muscle cells
glycogen
characteristics of the fasted state
low insulin : glycogen ratio. normal blood glucose concentration due to the change in ratio. muscle uses lipid. brain uses glucose and then at a later stage ketone bodies
what is there an increase of in the fasted state
concentration of NEFA, proteolysis, lipolysis, hepatic glucose output
what is there a decrease of in the fasted state
amino acid concentration when prolonged
characteristics of the fed state
high insulin:glucagon ratio. stored insulin released then you get 2nd phase insulin release. stop hepatic glucose output
what is there an increase of in fed state
glycogen, protein synthesis and lipogenesis
what is there a decrease of in fed state
gluconeogenesis, proteolysis
presentation of type 1 diabetes mellitus
Absolute insulin deficiency. Proteolysis with weight loss. Hyperglycaemia. Glycosuria with osmotic symptoms. Ketonuria
Insulin induced hypoglycaemia causes an increase in:
insulin, glucagon, catecholamines, cortisol and somatotrophin, HGO and lipolysis
What is insulin induced hypoglycaemia and how is it treated
Treatment induced complication. Increased insulin from SUBCUTANEOUS stores –> glucose uptake into muscle –> low plasma glucose concentration. TREATMENT: Increased INTRAMUSCULAR glucagon –> increased HGO, Glycogenolysis and gluconeogenisis and increased lipolysis –> increased plasma glucose
Insulin resistance and its effects
It resides in the liver, muscle and adipose tissue. Increase in LDL (dyslipidaemia), circulating NEFA, triglyceride. decrease in lipoprotein lipase activity, VLDL clearance and HDL cholesterol.
in T2DM what is there enough insulin to suppress
ketone production and proteolysis
what 2 pathways does insulin have an effect on
mitogenic pathway (MAPK) and metabolic pathway (PI3K-Akt)
compensatory hyperinsulinaemia
someone with insulin resistance makes enough insulin to maintain normal blood glucose
features of insulin resistance
hypertension (BP>135/80), high triglyceride, high ldl, fasting blood glucose > 6.0mmol/L, adipocytokines, inflammatory state, energy expenditure, large waist circumference
presentation of T2DM
Insulin resistance. 60-80% obese. Dyslipidaemia. Later insulin deficiency. Hyperglycaemia. Less osmotic symptoms. With complications
management of T2DM by controlling diet
Control total calorie intake. reduce fat, refined carbohydrate and sodium. increase complex carbohydrate and soluble fibre
