Lecture 5 - Insulin action Flashcards
What are the actions of insulin on glucose?
Decreases Hepatic Glucose Output (HGO) Increases muscle uptake
What are the actions of insulin on proteins?
Decreases proteolysis
What are the actions of insulin on lipids?
Decreases lipolysis and ketogenesis
What is the general action of insulin?
Growth Vascular effects Ovarian function Clotting - PAI-1 Energy expenditure - relation to leptin
Describe the GLUT-4 receptor
Muscle and adipose tissue Insulin responsive Lies in vesicles Recruited and enhanced by insulin Increases glucose uptake by 7x
What is the effect of insulin on proteolysis in muscles?
Insulin inhibits muscle protein breakdown, but when decreased with an increase of cortisol Protein > A.A. which causes O2> CO2 Then amino acids are transported out of the muscle cell
What is the effect of insulin on protein synthesis?
Increase in insulin, Growth hormone, IGF1 Causes A.A. to be synthesised into proteins
When is glucose present?
In blood - all the time, not just after meals as it is essential for brain function
How is glucose stored?
As glycogen in liver
What are the pathways of gluconeogenesis and amino acids?
Presence of glucagon causes a.a. to enter liver.
Proteins are turned into amino acids via glucagon presence or protein deficiency OR a.a. turn into proteins via presence of insulin OR a.a. turn into glucose via GLUCONEOGENESIS - presence of glucagon, catecholamines and cortisol and inhibited by insulin.
Glucose then released as HGO
What are the relative lasting times of the different fuel stores?
CHO - around 16 hrs (least amount present in body) Protein - 15 days Fats - 30-40 days (largest amount present in body)
What is the storage mechanism for triglycerides?
TG in the bood are broken down by lipase in presence of insulin, increasing glycerol levels Glucose enters the adipocytes via GLUT4 (^ insulin) NEFA enters the cell and is also formed from glucose NEFA joins with glycerol-3-P (made from glucose entering cell) NEFA + Glycerol-3-P = TRIGLYCERIDE TG can then either leave the cell as glycerol (insulin absent) OR as NEFA (presence of catecholamines, cortisol and growth hormone)
Describe the mechanism of hepatic gluconeogenesis after 10 hr fast (25% HGO)
Glycerol is taken up by the cells Converted to Glycerol3P which can be into TG OR can be converted into glucose, and released as HGO
What is the main source of energy for the brain?
Glucose and ketone bodies
What source of energy can the brain NOT use?
Fatty acids
What is the mechanism of NEFA conversion into ketone bodies?
NEFA enters cell (from omental adipocytes) Forms fatty acyl CoA With presence of glucagon & absence of insulin (shuttle in mitchondrial membrane) acetyl CoA > acetoacetate > acetone + 3 hydroxybutarate Then the ketone bodies leave the cell
Describe the mechanism of hepatic glycogenolysis after a meal
Glucose enters the cell G6P G6P into glycogen (presence of insulin) or the other way (presence of glucagon and catecholamine) G6P Glucose Glucose leaves the cell as HGO (when low hypoglycaemia)
Describe glycogen metabolism in muscles
Glycogen enters the cell and is turned into glucose Glucose enters cell in absence of GH, Cats, Cort and presence of insulin Glucose mostly converted into acetyl CoA (which also enters the cell) Acetyl CoA enters the Kreb cycle and O2 converted into CO2
What occurs in the fasted state?
LOW [INSULIN]:[GLUCAGON] [Glucose]= 3.0-5.5 mmol/litres ^ [NEFA] Decrease [amino acid] when prolonged ^ Proteolysis ^ Lipolysis ^ HGO from gluconeogenesis ^ Ketogenesis when prolonged Muscle uses lipids Brain uses glucose and later ketones
What occurs in the fed state?
Stored insulin released and then 2nd phase High [Insulin]: [glucagon] HGO stopped ^ Glycogen Decreased gluconeogenesis ^ protein synthesis Decreased proteolysis ^ lipogenesis
How does T1DM affect the mechanisms for energy?
Increased HGO leads to glucose and ketones release Muscle proteolysis occurs > a.a released Adipose cells cause lipolysis > glycerol and fatty acids
How does T1DM present in the patient?
Absolute insulin deficiency Proteolysis with weight loss HYPERGLYCAEMIA Glycosuria with osmotic symptoms Ketonuria
What are the main features of insulin induced hypoglycaemia?
^ insulin (due to subcutaneous injection) ^ glucagon ^ catecholamines, cortisol and GH (normal) Glucose enters muscle ^ HGO later with glycogenolysis and gluconeogenesis (brings patient out of hypo) Lipolysis increased
How are glucagon and insulin delivered to diabetic patients?
Intra-muscular glucagon Subcutaneous insulin NB: patients can throw up the meal after injecting insulin, so could cause hypoglycaemia
