Insulin action Flashcards
What effects does insulin have on glucose, proteins and lipids?
Glucose: decrease in HGO (hepatic glucose output) and increase muscle uptake
Lipids: decreased lipolysis and ketogenesis
Proteins: decrease proteolysis
What are the other effects of insulin?
- Lipoproteins
- Smooth muscle hypertrophy
- Ovarian function
- Clotting
- Energy expenditure
Glucose uptake into muscle and adipose cells?
Glucose is taken up with the GLUT-4 transporter, which is abundant in muscle and adipocytes.
Insulin stimulates GLUT 4- it has hydrophobic elements on the outside and a hydrophyllic core which allows glucose into the cell- it is insulin responsive.
Glut-4 sits in vesicles inside the cytoplasm. Insulin recruits them to move up to the membrane causing a 7 fold increase in glucose uptake.
The effects of insulin on protein (e.g on a muscle cell)?
Insulin stops proteolysis (and cortisol increases proteolysis- when we are stressed)
Amino acids could be oxidised in the muscle cells and insulin prevents oxidation of amino acids. Insulin increases the re-synthesis of proteins from the amino acid.
Somatotrophin and cortisol have contradicting effects.
Amino acid can get into circulation and move to the liver where it can be used to produce glucose
What is the effect of insulin on the liver?
Gluconeogenic (pyruvate and lactate) amino acids enter the liver via specific transporter channels.
Glucagon increases the uptake of amino acids by the liver.
Insulin stimulates proteinsynthesis in the liver.
The amino acids can however be used to make glucose by gluconeogenesis.
Insulin inhibits gluconeogensis
Somatotrophin, cortisol, catecholamines and glucagon increase gluconeogenesis. The glucose produced from gluconeogenesis can then enter circulation as HGO (hepatic glucose output)
What is the effect of insulin on adipocytes
Pink= blood vessel, yellow= adipocyte
Triglycerides come in vesicle and cannot enter the adipocyte directly. Lipoprotein lipase is stimulated by insulin. The triglyceride is broken down into glycerol and non-esterified fatty acids (NEFA) and absorbed into the adipocytes.
Glucose also enters the adipocytes and can be used to make NEFA. Glucose can also be broken dwon to make two glycerols and the fatty acid can stick to the glycerol to make triglyceride.
Insulin will stop lipolysis and the four counter-regulatory hormones will promote lipolysis. Insulin has 2 effects on fat, depending where it acts:
BLOOD- breaks down the fat so that it can enter adipocytes
ADIPOCYTE- promotes formation of triglyceride and storage of fat inhibits lipolysis.
What is the main architecture of our circulation system?
Blood reaches the gut and there is a portal system connecting the intestine (gut) to the liver. The blood passes through the liver for the absorbed food to be processed and any toxins to be dealt with.
Adipocytes in the gut are different in metabolic activity and endocrine regulation compared to the rest of the body. So, omental fat/ waist circumference is a simple indication of an individual’s risk of ischaemic heart disease.
How does the liver utilise glycerol?
Glycerol coming from adipocytes and food enters the liver. The glycerol is used to make triglycerides. The TGs can then enter lipoprotein particles.
Glycerol can also be used to make glucose- gluconeogenesis. Two glycerols can be stuck together and this is HGO (hepatic glucose output)
Glycerol can be used to make glucose but fat cannot re-enter the glucose pathway.
The brain is picky about its energy sources… what does it like to metabolise?
The brain can use glucose and ketone bodies
The brain CANNOT use FATTY ACIDS- this is because the brain is an organ that is predominantly made out of fat. Therefore it is not a good idea to have loads of enzymes that metabolise fats up there.
What is the effect on insulin on ketone body synthesis in the liver?
Fattu acids that are produced in lipolysis can enter the liver and used to make ketone bodies.
Insulin inhibits the conversion of fatty acyl CoA to ketone bodies
whereas glucagon promotes this
Ketone bodies will enter circulation and mainly be used by the muscles.
if someone has high insulin, then they should stop making ketone bodies.
High blood glucose and high keton bodies= insulin deficient
What are ketone bodies?
three water soluble molecules that are produced by the liver from fatty acids during periods of low food intake or carbohydrate restriction. These three molecules:
- acetone
- acetoacetic acid
- beta-hydroxybutyric acid
How does insulin affect glycogenolysis?
Glycogenolysis is the break down of glycogen.
Glucose enters the liver and is converted to glucose-6-phosphate. G6P can be converted into glycogen and insulin promotes the storage of glucose as glycogen.
Glucagon and catecholamines promote glycogenolysis- break down of glycogen into glucose to increase HGO. Therefore the 2 processes that support HGO are glycogenolysis and gluconeogenesis
What are the effects of insulin on glucose uptake by muscle cells?
Glucose enters the muscle by the GLUT4 transporter- insulin promotes this uptake.
Stress hormones tend to inhibit the uptake of glucose by GLUT4 and glucose can then be stored as glycogen in the muscle and can be used as a food source whenever it is required.
What is happening in the fasted state?
Low insulin: glycogen ratio
Blood glucose conc is normal (3.0-5.5 mmol/l). Increased NEFA and decreased amino acid when prolonged. Muscles use lipids, brain uses glucose and then ketone bodies.
There is an increase in: NEFA, proteolysis, lipolysis, HGO (glycogenolysis and gluconeogenesis)
There is a decrease in amino acid concentration
What is happening in the FED state?
High insulin: glycogen ratio
Stored insulin is released then you get 2nd phase insulin release. HGO stops.
There is an increase: glycogen, protein synthesis and lipogenesis
Decrease in: gluconeogenesis and proteolysis
What is the pathway of insulin?
It has 2 pathways;
- mitogenic pathway (anti-apoptosis)
- Metabolic pathway- this is where the insulin resistance is
The feedback loop for insulin production is mainly through blood glucose concentration- someone with insulin resistance will have compensatory hyperinsulinaen, enough to maintain a normal blood glucose. The high insulin is still harmful because there will be excess activity in the mitogenic pathway. The control of insulin concentration depends almost entirely on blood glucose concentration and not on downstream effects of the mitogenic pathway
What are the features of insulin resistance?
Hypertension
High triglyceride
Low HDL, High LDL
Fasting blood glucose > 6.0 mmol/l
Adipocytokines
Inflammatory state
Energy expenditure
High omental fat (large waist circumference)
