Absorptive/post-absorptive states Flashcards
What is the absorptive state?
Or fed state.
The pattern of energy metabolism due to high concentration of the nutrients in the blood as a result of absorption of the nutrients.
Some of the nutrients are used to meet immediate energy needs while the excess are stored for energy later.
What is the post-absorptive state?
Or fasted state.
A pattern of energy metabolism adopted between meals or during fasting.
Changes in the pattern of energy metabolism depends on the changes in blood concentration of insulin and other hormones.
What occurs in the absorptive state?
The absorbed nutrients are hexose sugars (glucose, galactose and fructose) and amino acids.
These nutrients go through the liver into circulation.
Other nutrients go into adipose tissues, muscles and other tissues.
Where do lipids go in the absorptive state?
Lipids go to the small intestines, then the lymph as chylomicrons, then venous blood, then adipose tissue.
How does the absorptive state occur?
Feeding causes uptake of glucose into circulation, which increases blood sugar.
The glucose enters the pancreas through GLUT2, which increases ATP.
What happens in the B-cells of the pancreas?
The increased ATP causes K+ channels to close, which causes membrane depolarisation.
This increase the intracellular concentration of Ca2+, and causes insulin exocytosis.
What is glycogen storage?
Glycogen is synthesised in the liver or muscles.
A disorder with glycogen storage causes accumulation of glycogen or change in structure of glycogen.
What is Pompeii disease?
An autosomal recessive disorder which affects the functioning of lysosomal acid a-glycosidase due to a mutation of GAA gene.
This causes cellular damage, as there is less glucose available.
Glycogen is accumulated in the lysosomes of liver and muscle cells rather than the cytoplasm.
What is insulin?
A hormone secreted by the pancreas.
Release of insulin is stimulated by the fed state - high concentration of glucose and amino acids in the blood. Insulin release is inhibited by the fasted state.
Hormones and neurotransmitters also influence insulin.
How does insulin work?
Insulin stimulates glucose transport by causing the recruitment, or translocation, of GLUT4 proteins from an intracellular vesicular compartment to the plasma membrane.
The transporter inserts into the plasma membrane, allowing uptake of glucose into the cell.
What does glucose do in the absorptive state?
Glucose and amino acids have increased absorption into the tissues, because insulin is increasingly secreted.
Glucose goes to the liver and the excess is converted to glycogen.
In adipose tissue, excess glucose is converted to fatty acids.
In muscles, excess glucose is converted to glycogen.
What does glucose do in the post-absorptive state?
There is less blood glucose so less insulin secretion.
Insulin-dependent tissues, e.g. muscles and adipose tissue rely on insulin.
Other tissues do not rely on insulin and can absorb glucose without insulin.
But when there is not much glucose available it can cause damage.
The body can change the pattern of metabolism so there is still a supply of glucose.
What happens a few hours after eating?
There is decreased blood glucose, so the body undergoes glucose-supplying reactions to use the tissues to provide glucose for energy supply.
What are glucose supplying reactions?
The liver uses stores of glycogen to release glucose into bloodstream.
From adipose tissue, triglycerides are broken down into glycerol to produce ATP.
From muscles, lactate can be produced, which can go to the liver to produce glucose by gluconeogenesis
What happens days after eating?
There is very low stores of glucose so the body undergoes glucose sparing reactions.
The brain and RBCs depend on glucose for energy.
A lack of glucose can cause brain damgage, coma and death.
What are glucose sparing reactions?
Adipose tissue had broken down triglycerides to form fatty acids which are stored in the liver.
Fatty acids then produce ketone bodies by ketogenesis, and are provided in blood stream as a precursor for energy, using a pathway to produce ATP.
All tissues can use ketone bodies as a source of ATP in the days after eating.
How does the brain function in the days after eating?
The brain uses glucose to produce ATP.
When there is limited supply, it can use ketone bodies to produce ATP.
The proportions of glucose and ketone bodies used depends on the supply of glucose and how much time elapsed since last eating.
What are the reactions in the post-absorptive state?
Glucose supplying reactions
Glucose sparing reactions
What are the features of glucose supplying reactions?
Glycogen is a store of glucose
Glycogenolysis is breakdown of glycogen.
Gluconeogenesis is production of glucose.
What are the features of glucose sparing reactions?
Fatty acids - short term.
Ketone bodies - long term, used to produce ATP.
What are the metabolic processes that would occur to maintain plasma glucose concentration during starvation?
Depletion of carbohydrate precursors
Increased gluconeogenesis (amino acids to glycerol).
After 48 hours, energy is supplied by ketone bodies and free fatty acids.
Prolonged starvation initiates protein catabolism - organ system dysfunction - breaking down muscles to generate energy.
What is type 1 diabetes mellitus?
Young onset.
Loss of B-cells, so cannot produce insulin.
Cannot utilise glucose so use other fuels.
Weight loss, ketoacidosis - ketones build up.
What is type 2 diabetes mellitus?
Prevalance increases with age.
Caused by insulin resistance.
Causes weight loss and ketoacidosis (build up of toxic ketones)
What are the characteristics of type 1 diabetes?
Cannot prevent type 1 diabetes
Autoimmune or genetic cause
No insulin produced
Cannot be reversed
What are the characteristics of type 2 diabetes?
Prevented through lifestyle changes
Can be reversed with early diagnosis
Partially functional pancreas
Some insulin produced but insulin resistance
Obesity or aging
What are the symptoms of diabetes?
Thirst, frequent urination, blurry vision
Requires a healthy lifestyle and medical treatment.
If untreated can cause complications.
How does diabetes affect the liver?
There is increased glycogenolysis - glycogen breakdown, as tissues are not receiving glucose, even though glucose is present in the bloodstream.
It can cause non-alcoholic fatty liver disease, as the excess glucose is being converted to fat and stored in the liver.
How does diabetes affect the muscles?
Gluconeogenesis from protein break down.
Causes muscle wasting.
How does diabetes affect fatty tissue?
There are increased fatty acids in circulation, because the cells cannot access the glucose so go into a post-absorptive state.
There is excess ketone because the liver cannot use lots of acetyl CoA as there is not enough substrate present, so forms ketone.
What are the tests for diabetes?
Glucose tolerance test - relies on metabolic pattern in absorptive state
Fasting blood sugar test - Procedure no eating 8 hours before, relies on metabolic pattern in post-absorptive state.
How does obesity affect diabetes testing?
Causes slower uptake of glucose - insulin resistance - increased plasma glucose.
Metabolic pattern is affected so the diabetes tests are not reliable.
So Haemoglobin A1C is more reliable for diagnosis and management.
What are the lifestyle modifications for type 2 diabetes treatment?
Balanced diet - more fibre rich fruits, wholegrain foods, less sweets and soda.
Exercising - aerobic and resistance exercise
What are the medications for type 2 diabetes treatment?
Oral - metformin, glipizide, pioglitazone, dapagliflozin, sitagliptin, acarbose.
Insulin - basal insulin, intermediate or long-acting forms.
What is glucose monitoring for type 2 diabetes?
HbA1C test - measures average blood glucose level over 2 months.
Fingerstick glucose testing daily or multiple per day.
What is GLP-1?
Glucagon-like peptide-1 is a peptide produced by the cleavage of proglucagon in pancreatic a-cells.
They activate GLP-1 receptors, which increases sinsulin release, and so decreases glucagon release.
This then delays gastric emptying.
What are GLP-1 agonists?
Agonists are used for the managment of type 2 diabetes and obesity.
They cause delayed gastric emptying, so there is appetite suppression, which aids with insulin resistance.
What is the Maillard reaction?
Non-enzymatic browning whcih makes food taste good.
This is when proteins and sugars combine and cause glycation.
How is glycation bad?
In the body, glycation triggers cytokines, which causes inflammation and oxidative stress, and then metabolic disorders.
What causes glycation?
Increased blood glucose levels but no uptake triggers glycation.
This causes diabetes complications because the glucose remains in vessels for too long.
What are microvascular complications of diabetes?
Eye - high blood glucose and blood pressure damages eye blood vessels, causes retinopathy, cataracts and glaucoma.
Kidney - high BP damages blood vessels and exccess glucose overworks the kidneys, causes nephropathy.
Neuropathy - hyperglycemia damages nerves in the PNS, causing pain or numbness.
What are macrovascular complications of diabetes?
Brain - increased risk of stroke, cognititive impairment.
Heart - high BP and insulin resistance increases risk of CHD.
Extremeties - peripheral vascular disease from narrowing of blood vessels, reduced blood flow to feet, causing wounds to heal slowly - gangrene.
How does glucose damage the lumen?
When there is lots of glucose in the lumen it affects the pH to be more acidic.
This affects the lining of the lumen and causes many side effects.
In chronic diabetes all vessels are affected like this.
What is retinopathy?
Growth of poor quality new blood vessels in the retina.
Macular oedema, which can lead to sever vision loss.
Blindness
What is neuropathy?
Decreased sensation in hands and feet, damages blood vessels.
Causes diabetic foot ulcers, which might go unnoticed.
There is delayed healing because of blood sugar, which can lead to secondary infection and requires amputation.
