Blood Glucose Homeostasis

Pancreatic Hormones – Glucagon and Insulin:

• The pancreas produces two main hormones involved in regulating blood glucose:
  • Insulin (produced by beta cells)
  • Glucagon (produced by alpha cells)

Post-Meal: Regulation of Blood Glucose

Step 1: Post-Meal Rise in Blood Glucose Levels

• After eating, glucose enters the bloodstream, causing blood glucose levels to rise.
• Elevated blood glucose stimulates beta cells in the pancreas to release insulin.

Role of Insulin

1. Insulin facilitates the transport of glucose into the body’s cells, by stimulating the insertion of GLUT4 glucose transporters into the cell membranes of the body’s cells.
   • • Insulin binds to insulin receptors on cell membranes.
     • Triggers GLUT 4 vesicles to move to the membrane and insert.
   • Cells are then able to uptake glucose from the bloodstream.
     • Glucose is water-soluble and need a membrane transporter to enter cells.
     • Prevents cell starvation in glucose, the vital energy source (required for ATP production)..
2. Insulin facilitates ATP production:
   • Glucose is used by cells to generate ATP through:
     • Anaerobic cellular respiration (Glycolysis) in which Glucose → Pyruvate + 2 ATP
     • Aerobic cellular respiration (Krebs/Citric Acid/Tricarboxylic Acid Cycle) and Electron Transport Chain in which Glucose is broken down to produce 30-32 ATP
   • Without insulin, glucose remains in blood, leading to hyperglycemia, and cells would be deprived of energy, impairing ATP production.
3. Insulin stimulates glycogenesis (glycogen synthesis) in liver and skeletal muscle.
   • Glycogen is a fuel storage molecule that can be broken down into glucose.
4. Insulin also promotes the uptake of amino acids and lipids by cells which supports
   • Supports protein synthesis, cellular growth and maintenance and healing
     • Insulin influences gene expression and growth regulation!
5. Insulin additionally promotes triglyceride synthesis in adipocytes (for storage of lipids as triglycerides)

Outcome:
• Blood glucose levels decrease back to normal, maintaining homeostasis.

Between Meals: Low Blood Glucose

• Blood glucose levels drop as cells use glucose for energy.
• When levels get low, especially during hunger, fasting, or starvation:
  • Alpha cells in the pancreas are stimulated to secrete glucagon.

Role of Glucagon

• Works in opposition to insulin.
• When blood glucose levels are low, glucagon is secreted by pancreatic alpha cells.
•  Glucagon:
  1. Signals the liver to produce and release glucose.
  2. Triggers gluconeogenesis and glycogenolysis:
     • • Neo- = new, gluco- = glucose, -genesis = creation.
     • Liver gluconeogenesis produces additional glucose from:
       1. Proteins (via protein breakdown)
       2. Fats/triglycerides (via lipolysis)
     • Liver glycogenolysis breaks down glycogen to produce even more glucose.
       • Glycogen stores (glycogenolysis)

Outcome:

• Glucose enters the bloodstream.
• Blood glucose levels return to normal, ensuring cells continue to receive energy.
• Ensures cell function and brain energy supply during fasting.
• Normal Blood Glucose Level Range:  70 – 110 mg/dL

Summary

• Insulin lowers blood glucose after meals.
• Glucagon raises blood glucose during fasting or low-glucose states to maintain blood glucose levels within the normal range (70-110mg/dL) and therefore maintain homeostasis.
• Both hormones act oppositely to maintain blood glucose within the healthy range.
• This dynamic regulation maintains blood glucose levels within a narrow, healthy range, vital for normal cellular function and energy homeostasis.