Endocrine Control of Metabolism

• What is energy balance in metabolism?

  Energy balance is the relationship between energy intake (from food) and energy expenditure (for basal metabolism, physical activity, and thermogenesis). Maintaining energy balance is essential for homeostasis.
• What are the major metabolic pathways involved in energy metabolism?

  1. Glycolysis – Breakdown of glucose to pyruvate
  2. Gluconeogenesis – Synthesis of glucose from non-carbohydrate sources
  3. Glycogenesis – Formation of glycogen from glucose
  4. Glycogenolysis – Breakdown of glycogen to glucose
  5. Lipogenesis – Conversion of excess glucose to fatty acids
  6. Lipolysis – Breakdown of triglycerides into fatty acids and glycerol
  7. β-oxidation – Fatty acid breakdown into acetyl-CoA
  8. Ketogenesis – Formation of ketone bodies from fatty acids
  9. Protein catabolism – Breakdown of proteins into amino acids (for gluconeogenesis or energy)
• Which hormones are key regulators of metabolic pathways?

  • Insulin
  • Glucagon
  • Adrenaline
  • Cortisol
  • Growth hormone
  • Thyroid hormones (T3, T4)
• What is the overall metabolic role of insulin?

  Insulin is an anabolic hormone that promotes energy storage by:

  • Increasing glucose uptake (especially in muscle and adipose tissue)
  • Stimulating glycogenesis, lipogenesis, and protein synthesis
  • Inhibiting gluconeogenesis, lipolysis, and proteolysis
• Which metabolic pathways does insulin stimulate?

  • Glycogenesis
  • Lipogenesis
  • Protein synthesis
  • Glycolysis
• Which metabolic pathways does insulin inhibit?

  • Gluconeogenesis
  • Glycogenolysis
  • Lipolysis
  • Ketogenesis
  • Proteolysis
• What is the overall metabolic role of glucagon?

  Glucagon is a catabolic hormone that promotes energy mobilisation during fasting by:

  • Stimulating glycogenolysis and gluconeogenesis in the liver
  • Promoting lipolysis in adipose tissue
  • Encouraging ketogenesis
• How does adrenaline (epinephrine) affect metabolism?

  Adrenaline acts during stress/exercise to:

  • Stimulate glycogenolysis (in liver and muscle)
  • Increase lipolysis
  • Inhibit insulin secretion
  • Enhance glucagon effects
• What is the role of cortisol in metabolism?

  Cortisol increases blood glucose during prolonged fasting or stress by:

  • Promoting gluconeogenesis and proteolysis
  • Enhancing lipolysis
  • Inhibiting glucose uptake (anti-insulin effect)
• What is the metabolic effect of growth hormone (GH)?

  GH promotes growth and energy availability by:

  • Increasing lipolysis
  • Reducing glucose uptake (anti-insulin effect)
  • Stimulating protein synthesis
• What are the metabolic effects of thyroid hormones (T3 and T4)?

  • Increase basal metabolic rate (BMR)
  • Stimulate carbohydrate and fat metabolism
  • Enhance protein turnover
  • Potentiate effects of catecholamines (e.g., adrenaline)
• What are the key metabolic characteristics of the fed state (after eating)?

  • High insulin, low glucagon
  • Glucose is the primary fuel
  • Increased glycogenesis, lipogenesis, protein synthesis
  • Decreased gluconeogenesis, lipolysis
• What are the key metabolic characteristics of the fasting state?

  • Low insulin, high glucagon
  • Glucose conservation and alternate fuel use
  • Increased gluconeogenesis, glycogenolysis, lipolysis, ketogenesis
  • Decreased glycogenesis, protein synthesis
• During fasting, how is blood glucose maintained?

  • Early fasting: Glycogenolysis (liver)
  • Prolonged fasting: Gluconeogenesis (from lactate, glycerol, amino acids)
• Which two main hormones maintain plasma glucose homeostasis?

  • Insulin (from pancreatic β-cells) — lowers blood glucose.
  • Glucagon (from pancreatic α-cells) — raises blood glucose.These hormones act antagonistically to maintain glucose within a narrow range.
• How does insulin decrease blood glucose levels?

  • Increases glucose uptake by muscle and adipose tissue via GLUT4 transporters.
  • Stimulates glycogenesis in the liver and muscle.
  • Inhibits gluconeogenesis and glycogenolysis in the liver.
  • Promotes lipogenesis and protein synthesis.
• How does glucagon increase blood glucose levels?

  • Stimulates glycogenolysis in the liver.
  • Stimulates gluconeogenesis from non-carbohydrate substrates.
  • Inhibits glycolysis in the liver to conserve glucose.
  • Promotes lipolysis in adipose tissue to provide alternative energy.
• What is the role of the liver in glucose homeostasis?

  The liver acts as a glucose buffer:

  • Stores glucose as glycogen postprandially (after eating).
  • Releases glucose via glycogenolysis and gluconeogenesis during fasting.
  • Responds to insulin and glucagon to regulate blood glucos
• What is gluconeogenesis and when is it activated?

  Gluconeogenesis is the synthesis of glucose from non-carbohydrate sources (e.g., lactate, glycerol, amino acids).It is activated during prolonged fasting, low carbohydrate intake, or glucagon dominance.
• What are the effects of adrenaline and cortisol on blood glucose?

  • Adrenaline: Increases glycogenolysis in muscle and liver; promotes lipolysis.
  • Cortisol: Enhances gluconeogenesis and reduces glucose uptake in tissues.Both hormones help raise blood glucose during stress or fasting.
• What is the fed state vs. the fasting state in glucose regulation?

  • Fed state (postprandial): High insulin, low glucagon → glucose uptake & storage.
  • Fasting state: Low insulin, high glucagon → glucose production & release.
• What is the role of GLUT4 transporters in glucose homeostasis?

  GLUT4 is an insulin-sensitive glucose transporter in skeletal muscle and adipose tissue.Insulin triggers its translocation to the cell membrane, facilitating glucose uptake.
• How does the brain regulate plasma glucose concentration?

  The hypothalamus detects changes in blood glucose and signals appropriate hormonal responses (e.g., stimulating glucagon, inhibiting insulin) to maintain glucose supply, especially to the brain.
• What is diabetic ketoacidosis (DKA)?

  Diabetic ketoacidosis (DKA) is a life-threatening metabolic complication of diabetes mellitus, primarily type 1, characterized by hyperglycemia, ketosis, and metabolic acidosis due to an absolute or relative deficiency of insulin.
• How does lack of insulin affect glucose uptake?

  Insulin is required for glucose uptake into insulin-sensitive tissues (e.g., muscle and adipose). Without insulin, glucose cannot enter cells efficiently, leading to hyperglycaemia despite intracellular glucose starvation.
• What triggers lipolysis in the absence of insulin?

  In the absence of insulin, the inhibitory effect on hormone-sensitive lipase is removed, leading to increased lipolysis and release of free fatty acids (FFAs) from adipose tissue.
• How do free fatty acids contribute to DKA?

  FFAs released during lipolysis are taken up by the liver and converted into ketone bodies (acetoacetate and β-hydroxybutyrate) via β-oxidation due to the lack of insulin and high glucagon levels.
• Why does ketogenesis increase in DKA?

  Low insulin and high glucagon stimulate hepatic ketogenesis. Acetyl-CoA from β-oxidation is diverted into ketone body synthesis instead of the Krebs cycle due to oxaloacetate depletion.
• What are the main ketone bodies involved in DKA?

  The main ketone bodies are acetoacetate, β-hydroxybutyrate, and acetone. Acetoacetate and β-hydroxybutyrate are acidic and contribute to the metabolic acidosis seen in DKA.
• How does ketone body accumulation lead to acidosis?

  Accumulated ketone bodies lower blood pH, resulting in metabolic acidosis. The body’s buffering systems are overwhelmed, leading to compensatory hyperventilation (Kussmaul respiration) to expel CO₂.
• Why does dehydration occur in DKA?

  Hyperglycemia exceeds the renal threshold, leading to glucosuria. Glucose in the urine causes osmotic diuresis, resulting in severe dehydration and electrolyte loss.
• What are common symptoms of DKA?

  Symptoms include polyuria, polydipsia, dehydration, nausea, vomiting, abdominal pain, fruity-smelling breath (acetone), Kussmaul breathing, and altered mental status.
• What are the three biochemical hallmarks of DKA?

  1. Hyperglycemia
  2. Metabolic acidosis (low pH and bicarbonate)
  3. Ketosis (elevated serum and urine ketones)