01-02-22 - Metabolic Changes in Health and Disease Flashcards
Learning outcomes
- Describe the metabolic changes associated with short-term and long-term fasting
- Describe the role of key hormones involved in metabolism: insulin and glucagon
- Describe the location and cell types of insulin and glucagon secretion and the major metabolic effects they each illicit on tissues
- Briefly describe the effects of adrenalin/noradrenalin on metabolism
- Define the two main types of diabetes mellitus and summarise the metabolic/health consequences of chronic hyperglycaemia
How much energy is lost as heat?
How does body weight remain stable?
When is the storage of excess body fat healthy?
What 5 diseases can obesity and chronic low grade systemic inflammation increase the risk of?
- 60% of total energy is lost as heat (every reaction generates heat)
- When energy intake = energy output, body weight remains stable
- Apart from periods of growth (childhood/adolescence) storage of excess fat is unhealthy
• Obesity and Chronic low grade systemic inflammation (chronic inflammation) can increase the risk of:
1) Cancer
2) CV disease
3) Osteoarthritis
4) Metabolic syndrome
5) Type II diabetes
What 4 factors regulate food intake?
• Factors that regulate food intake:
1) Brain
• Hypothalamus
• Positive and negative feedback systems
• Brain stem
2) Hormones • Positive and negative stimulation • Insulin inhibits hunger • Glucagon/ghrelin/adrenalin stimulate hunger • Thyroxine levels
3) Nutrient signals
• Nutrient sensors can increase blood glucose, amino acids and fatty acids, which can inhibit hunger
4) Neural signals
• Vagal nerves between gut and brain (hunger centre)
• Stretch receptors
What is the role of hypoglycaemic hormones?
What is 1 example?
What is the role of hyperglycaemic hormones?
What are 4 examples?
- Hypoglycaemic hormones are anabolic and act to decrease blood glucose through fuel storage
- An example of this is insulin, which encourages cells to take up glucose
- Hyperglycaemic hormones are catabolic, and act to increase blood glucose levels by mobilising energy reserves
• Examples:
1) Glucagon
2) Adrenalin
3) Cortisol (not directly related to absorptive/postabsorptive processes)
4) Growth hormone (not directly related to absorptive/postabsorptive processes)
What is the aim of metabolic homeostasis?
Why is this?
What is glucose sparing?
What is the normal range for blood glucose?
What 3 processes does glucose use to regulate this?
- The aim of metabolic homeostasis is to ensure constant supply of glucose for the brain (60% of all glucose is used by the brain)
- This is because the brain has no glycogen stores, and can’t utilise fatty acids for energy due to the blood brain barrier
- Glucose sparing is when blood glucose levels are low and other tissues swap to alternate fuel sources so there is enough for the brain
- Normal range of blood glucose concentration is 4-7mmol/L or 70-110mg/dL
• Liver regulated blood glucose through:
1) Glycogenesis
2) Glycogenolysis
3) Gluconeogenesis
How many calories are in total body stores?
How long can this last?
What 4 things occur in the first days of starvation?
- Body stores have a total of about 162,000 kcal
- These stores can last 1-3 months, based on activity
• In the first days of starvation:
1) Carbohydrates stores will last 1 day or less – blood glucose will fall
2) Proteins can yield glucose (deamination and gluconeogenesis) but ned to be preserved as much as possible
3) Muscle shifts to using fatty acids as primary fuel (glucose sparing for the brain)
4) Triglycerides have limited ability to be converted to glucose
What 5 things occur in later stages of starvation (>3 days)?
• After more than 3 days of starvation:
1) Ketone bodies build up (consequence of fatty acid breakdown to acetyl-coa and reduced activity of the citric acid cycle)
2) Over the first few days, the brain becomes more tolerant to lower glucose concentration, and uses ketone bodies
3) Over time the brain gradually increases the use of ketone bodies – need for glucose Is lowered
4) Preserves valuable protein reserves of protein, as need for amino acids to fuel gluconeogenesis reduced (muscle preserved)
5) Maintaining protein levels is important for survival
What are the endocrine cells of the pancreas?
Where are they found?
What mass do they make up of the pancreas?
What 4 hormones are produced by what 4 cells?
What are these hormones responsible for?
What is a disorder concerning these cells?
What are the exocrine secretions of the pancreas?
- The endocrine cells of the pancreas are the Islets of Langerhans, which are found embedded within exocrine tissue (acinar cells)
- These endocrine cells make up 1-2% of the total pancreas mass
- Islets of Langerhans produce hormones:
- Alpha cells produce glucagon
- Beta cells produce insulin
- Delta cells produce somatostatin
- PP cells produce pancreatic polypeptide
- These hormones are essential for the regulation of blood glucose
- A key disorder of these cells is diabetes mellitus, which is caused by the immune system killing insulin-producing beta cells
- The exocrine function of the pancreas is the secretion of digestive enzymes and bicarbonate
- The exocrine function of the pancreas is the secretion of digestive enzymes and bicarbonate
What does insulin direct?
What kind of hormone is it?
What 3 things stimulate β-cells of the pancreas to secrete insulin?
What 5 things does insulin stimulate in target cells when it binds to membrane receptors?
- Insulin directs the events of the absorptive state
- It is a hypoglycaemic hormone
• Β-cells stimulated to secrete insulin in response to:
1) Rising blood glucose levels
2) Glucose-dependent insulinotropic peptide (GI tract hormone)
3) Parasympathetic nervous system
• When insulin binds membrane receptors on target cells, stimulating:
1) Translocation of GLUT transporters
2) Facilitated diffusion – 20-fold increase in glucose uptake
3) Glycogen synthesis (liver/muscle)
4) Glycolysis
5) Triglyceride and protein synthesis (in fat and muscle)
When does glucagon control blood glucose levels?
What kind of hormone is glucagon?
When do α-cells of the pancreas secrete glucagon?
How is glucagon inhibited?
What does glucagon mainly act on?
What 2 processes does it stimulate?
How is lipolysis stimulated?
How is lipogenesis stimulated?
- Glucagon controls blood glucose levels in the postabsorptive / fasting state
- Glucagon is a hyperglycaemic hormone
- Α-cells in the pancreas secrete glucagon in response to low blood glucose concentration and rising levels of amino acids
- Glucagon is inhibited by high blood glucose and insulin
• Glucagon acts mainly on the liver, stimulating:
1) Glycogenolysis
2) Gluconeogenesis
- Lipolysis occurs in adipose tissue following low insulin levels
- Insulin stimulates lipogenesis
What determines the state of metabolism?
What 4 processes do high levels of insulin stimulate?
What 3 processes do high levels of glucagon stimulate?
- Circulating levels of insulin and glucagon determine the state of metabolism
- High levels of insulin stimulate:
1) Glucose oxidation
2) Glycogen synthesis
3) Fat synthesis
4) Protein synthesis
• High levels of glucagon stimulate:
1) Glycogenolysis
2) Gluconeogenesis
3) Ketogenesis
Other hyperglycaemic hormones.
What are adrenalin and noradrenaline synthesised by?
What too they target?
What 2 actions do they have?
Where is cortisol generated?
What does cortisol do?
How does the sympathetic nervous system affect glucose levels?
What can it also supply?
What 2 hormones does it also produce?
What action do they both have?
- Adrenalin and noradrenalin (catecholamines) are synthesised by the adrenal medulla
- They target mainly muscle for glycogenolysis
• Adrenalin and noradrenalin:
1) Lowers glucose uptake by muscle, and causes them to metabolise fatty acids instead (glucose sparing)
2) Increase glucagon secretion/inhibit insulin secretion
- Cortisol is produced in the cortex of the adrenal gland
- Cortisol is the primary stress hormone that increases glucose in the blood stream for increased use by the brain and for availability in tissue repair
- The sympathetic nervous system plays a crucial role in increasing glucose concentration
- Sympathetic fibres can also supply adipose tissue
• The sympathetic nervous system also produces:
1) Growth hormone
2) Thyroxine
• They both enhance gluconeogenesis and mobilise stores
What is diabetes mellitus?
How is it caused?
What is it characterised by?
What 3 things are those with diabetes at significant risk of?
- Diabetes is a chronic metabolic disease resulting from deficient secretion or action of insulin
- It is characterised by elevated blood glucose/chronic hyperglycaemia
• Those with diabetes are at significant risk of:
1) CV disease
2) Neuropathy
3) Microvascular damage – blood vessels, eyes, kidneys
What % of diabetes cases are Type 1?
What causes it?
When does onset commonly occur?
What are 2 potential causes of Type 1 diabetes?
What is required when dealing with type 1 diabetes?
How is it treated?
- Type 1 (insulin dependent) diabetes makes up about 10% of cases of diabetes
- It is an autoimmune condition in which β-cells in the pancreas are destroyed, so no insulin is released
- Usually, juvenile onset
• Causes of type 1 diabetes are not fully understood, may be:
1) Genetic predisposition (HLA genes)
2) Environmental trigger
- Type 1 diabetes requires close monitoring of blood glucose levels and diet
- Treated with insulin injections
What % of diabetes cases are type 2?
When it the typical onset?
What are 2 causes?
What happens to tissue sensitivity to insulin?
What are the 2 treatments?
- About 90% of diabetes cases are type 2 diabetes (non-insulin dependent)
- Usually late onset (but getting younger)
• Causes of type 2 diabetes:
1) Mostly associated with lifestyle (poor diet/lack of exercise/obesity)
2) Genetic component
- Tissues become insensitive to the effects of insulin (insulin resistance)
- Treatments:
1) Lifestyle changes (diet and exercise)
2) Hypoglycaemic drugs e.g metformin
What are 6 health consequences of chronic hyperglycaemia?
• Health consequences of chronic hyperglycaemia:
1) Lack of insensitivity to insulin
• leads to increase in blood glucose concentration
2) Excess glucose (>200mg/dl) cannot be reabsorbed by kidneys
• Glucose is excreted in the urine
3) Dehydration
• Osmotic pressures caused by glucose in renal tubules leads to decrease in water absorption.
• Can cause:
1) Polyuria
2) Intracellular/extracellular dehydration
3) Increased thirst and hunger
4) Tissue injury • Prolonged hyperglycaemia can lead to damage in blood vessels • This can cause poor circulation, and increase the risk of: 1) MI 2) Stroke 3) Kidney disease 4) Blindness 5) Ischaemia 6) Gangrene of extremities
5) Peripheral neuropathy
• Loss of sensation
6) Autonomic nerve dysfunction
• Bladder control
• Cardiovascular reflexes
What are 3 metabolic consequences of chronic hyperglycaemia?
• Metabolic consequences of chronic hyperglycaemia:
1) As tissues are not influences by insulin, metabolism to that seen in prolonged fasting/starvation is common
2) High glucose availability, but glucose can not be utilised
3) Increased utilisation of fats:
• Glycolysis slows
• Gluconeogenesis stimulated using amino acids
• New glucose and ketone bodies from fatty acid β-oxidation enter the blood
• Metabolic acidosis due to the increase in ketone bodies (
