Lecture 21 - Absorptive state Flashcards
What is the absorptive state?
- This is the fed state. It occurs after eating food and your body is digesting the food and absorbing the nutrients (via blood and lymph)
- Absorbed nutrient s enter the portal blood and first port of call is the liver (Monosaccharides, amino acids, lipids)
What are the hormone-sensitive tissues of energy metabolism?
Liver, muscle, adipose tissue
What is the post-absorptive state?
Fasting state, the nutrients have already been absorbed, digested and stored.
How does the body utilise energy stores during the post-absorptive state?
- Glucose-supplying reactions (reactions which generate glucose ~750 c/day)
- Glucose-sparing reactions (reactions which generate other energy substrates such as FA’s and ketone bodies ~2500 c/day)
- Reactions essential for preserving plasma glucose levels for the brain
What are the glucose-supplying reactions during the post-absorptive state?
- Glucose is produce in the liver by:
1. Glycogenolysis
2. Gluconeogenesis (new synthesis)
What are the control of glucose-supplying reactions?
- Fall in insulin levels
2. Increase in other hormones
What hormones increase during glucose-supplying reactions?
- Epinephrine increases glycogen breakdown in muscle, adipocytes and liver.
- Glucagon increases glycogen breakdown and gluconeogenesis in the liver.
- Cortisol increases gluconeogenesis in the liver and decreases glucose uptake.
- Growth hormone decreases glucose uptake.
How is the absorptive state controlled by hormones?
- Switch from post-absorptive to absorptive state due to increased glucose and insulin in the blood.
- insulin - secreted by beta-cells of the islets of langerhans in the pancreas. Trigger is high blood glucose and amino acids.
- GLUT-2 is the transporter responsible for beta-cell glucose uptake. This triggers the generation of ATP from glucose metabolism and Ca2+ influx.
- the raised intracellular Ca2+ causes insulin exocytosis
What is the feedback control of insulin after a meal?
blood glucose concentration increases (absorptive state) -> Insulin secretion stimulated -> glucose uptake into cells (GLUT-4) -> blood glucose concentration falls -> stimulus for insulin secretion removed -> blood insulin concentration falls (Post-absorptive state)
How does insulin regulate access of glucose into muscle and fat?
- Muscle and adipose tissue need insulin for glucose entry to cells.
- GLUT4 is a glucose transporter stored within the cell. Insulin stimulates translocation to the plasma membrane.
- In diabetes, high extracellular, but low intracellular, glucose disposal into these tissues.
- Insulin promotes glucose disposal into these tissues.
What are the effects of insulin on the liver, adipose and muscle tissue?
- portal circulation
- Activating - Glucokinase, glycogen synthase, phosphofructokinase, pyruvate dehydrogenase, acetyl CoA carboxylase, Fatty acid synthase
What are the effects of insulin on the liver, adipose and muscle tissue?
- portal circulation
- Activating - Glucokinase, glycogen synthase, phosphofructokinase, pyruvate dehydrogenase, acetyl CoA carboxylase, Fatty acid synthase
- Inhibitory - Glycogen phosphorylase, glucose-6-phosphate
- Activating - pyruvate dehydrogenase, acetyl CoA carboxylase, Lipoprotein lipase
- Inhibitory - Hormone sensitive TG lipase
Describe Type I diabetes
- Young onset, destruction of beta cells and loss of insulin. Severe metabolic derangement due to inability to utilise glucose (and the reduced cellular energy).
- Switch to other fuels (amino acids, lipids) leads to marked weight loss and metabolic disturbance (hyperlipidaemia, ketacidosis).
Describe type II diabetes
Prevalence increases with age. Insulin levels are usually normal or high but have reduced action (i.e. insulin resistance). treated with lifestyle (diet, exercise, weight loss), tablets (insulin stimulators or potentiators) or insulin. Less severe metabolic derangement since some insulin action is still present. Causes long-term damage due to high glucose level and lipid abnormalities.
- Obesity is found in approx 55% of patients with type 2 diabetes
- decreased glycogen synthesis
- Increased glycogenolysis
- Decreased glucose uptake
- Increased lipolysis
- Increased extracellular glucose
- Breakdown of protein to amino acids as substrates for gluconeogenesis (leads to muscle wasting)
Summary of metabolic derangement for type 2 diabetes?
- Level of glucose in blood is high because uptake is not stimulated.
- Further compounded by lack of insulin mediated inhibition of glycogenolysis and lipolysis.
- Increased circulating fatty acids directed to the liver where they are used in beta-oxidation. This liberates energy and acetyl CoA, in diabetes the high level of acetyl CoA generated in hepatocytes inhibits the citric acid cycle and acetyl CoA is pushed towards ketogenesis.
- These ketones are then used as an energy source in extra hepatic tissues where it is reconverted back to acetyl CoA and used to produce energy and even lipogenesis (especially in the brain).
- As ketones are acidic in nature this leads to acidosis.
- Formation increases 20-fold in uncontrolled type 1 diabetes.
- Acetone is the breakdown product of ketone bodies.
- Volatile gas that escapes on breath.
- Characteristic smell.
