Endocrine Regulation of Metabolism

Overview of Metabolic Hormones - Metabolic Orchestra

• Hormones act as a "metabolic orchestra," coordinating fuel storage and mobilization.
• Key Regulators:
  • Insulin: Anabolic; ↓ blood glucose, ↑ storage (glycogen, fat, protein).
  • Glucagon: Catabolic; ↑ blood glucose (glycogenolysis, gluconeogenesis).
  • Cortisol: Permissive; ↑ gluconeogenesis, protein catabolism, lipolysis.
  • Thyroid Hormones (T3/T4): ↑ Basal Metabolic Rate (BMR), ↑ O2 consumption.
  • Growth Hormone (GH): Anabolic (protein); ↑ lipolysis, anti-insulin effects.
  • Adrenaline: Catabolic; rapid glucose mobilization (glycogenolysis), ↑ lipolysis.

⭐ Hormones primarily regulate metabolism by altering enzyme activity, enzyme synthesis, or substrate availability.

Insulin's Role in Metabolism - The Anabolic Architect

The principal anabolic hormone, secreted by pancreatic β-cells, primarily responding to hyperglycemia. Promotes storage of glucose, fats, and proteins.

• Carbohydrate Metabolism:
  • ↑ Glucose entry into cells: Skeletal muscle, adipose tissue (via GLUT4 translocation).
  • ↑ Glycogenesis: Liver & muscle convert $Glucose \rightarrow Glycogen$.
  • ↓ Glycogenolysis: Inhibits glycogen breakdown.
  • ↓ Gluconeogenesis: Suppresses new glucose synthesis in the liver.
  • ↑ Glycolysis: Enhances glucose utilization for energy.
• Fat Metabolism:
  • ↑ Lipogenesis: Promotes fatty acid synthesis & triglyceride formation (liver, adipose tissue).
  • ↓ Lipolysis: Inhibits hormone-sensitive lipase, reducing fatty acid release from adipocytes.
  • ↑ VLDL formation in the liver.
• Protein Metabolism:
  • ↑ Amino acid uptake by cells.
  • ↑ Protein synthesis (ribosomal activity).
  • ↓ Protein catabolism (anti-proteolytic effect).

⭐ GLUT4, found in skeletal muscle and adipose tissue, is the primary insulin-responsive glucose transporter. Its translocation to the cell membrane is insulin-dependent.

Counter-Regulatory Hormones - Balancing Act

• Oppose insulin action, primarily to ↑ blood glucose levels during hypoglycemia or stress.
• 📌 Mnemonic: CAGE (Cortisol, Adrenaline/Epinephrine, Glucagon, Growth Hormone).
• Glucagon:
  • Secreted by: Pancreatic α-cells.
  • Stimulus: ↓ Glucose, ↑ amino acids.
  • Key Actions: ↑ Hepatic glycogenolysis, ↑ gluconeogenesis, ↑ ketogenesis.

  ⭐ Glucagon's primary site of action is the liver, promoting glycogenolysis and gluconeogenesis.

• Epinephrine (Adrenaline):
  • Secreted by: Adrenal medulla.
  • Stimulus: Stress, hypoglycemia.
  • Key Actions: ↑ Glycogenolysis (liver & muscle), ↑ gluconeogenesis, ↑ lipolysis, ↓ insulin secretion.
• Cortisol:
  • Secreted by: Adrenal cortex.
  • Stimulus: Stress (via ACTH).
  • Key Actions: ↑ Gluconeogenesis (hepatic), ↑ proteolysis (muscle), ↓ peripheral glucose uptake (induces insulin resistance), ↑ lipolysis. Permissive effect.
• Growth Hormone (GH):
  • Secreted by: Anterior pituitary.
  • Stimulus: Hypoglycemia, stress, sleep.
  • Key Actions: ↓ Peripheral glucose uptake, ↑ lipolysis, ↑ hepatic glucose output (indirectly). Diabetogenic in excess.

Metabolism in Different States - Fuel Management

• Fed State (Postprandial; up to ~4h):
  • Hormones: ↑ Insulin (dominant), ↓ Glucagon.
  • Processes: Glucose uptake, glycogenesis (liver, muscle), lipogenesis (adipose, liver), protein synthesis.
  • Primary Fuel: Dietary glucose.
• Early Fasting (Post-absorptive; ~4-18h):
  • Hormones: ↓ Insulin, ↑ Glucagon, ↑ Epinephrine, ↑ Cortisol (basal).
  • Processes: Hepatic glycogenolysis (major glucose source), gluconeogenesis (hepatic, renal; from lactate, alanine, glycerol), lipolysis begins.
  • Fuels: Glucose (brain, RBCs), FFAs (muscle, liver).
• Prolonged Fasting/Starvation (>18-24h):
  • Hormones: ↓↓ Insulin, ↑↑ Glucagon, ↑ Cortisol.
  • Processes: Gluconeogenesis (maintains blood glucose), ↑↑ lipolysis (adipose), ↑ ketogenesis (liver from FFAs: β-hydroxybutyrate, acetoacetate). Muscle protein catabolism minimized (protein sparing).
  • Fuels: FFAs (major), ketone bodies (brain, muscle), glucose (obligate users).

  ⭐ During prolonged starvation, the brain adapts to utilize ketone bodies as a major fuel source, sparing glucose.

High‑Yield Points - ⚡ Biggest Takeaways

• Insulin: Primary anabolic hormone, promotes glucose uptake (via GLUT4 in muscle/adipose) and storage.
• Glucagon: Main catabolic hormone, stimulates glycogenolysis and gluconeogenesis, raising blood glucose.
• Cortisol: Exerts permissive effects on glucagon/epinephrine; promotes proteolysis and lipolysis.
• Growth Hormone (GH): Has anti-insulin (diabetogenic) effects; stimulates lipolysis.
• Thyroid Hormones (T3/T4): Increase Basal Metabolic Rate (BMR) and potentiate catecholamines.
• AMPK: Key cellular energy sensor, activated by ↑AMP/ATP ratio, promoting catabolism.