Understanding Incretins and GLP-1

Oct 6, 2024

Lecture Notes on Incretins and GLP-1

Background on Incretins and GLP-1

  • Incretins: Gut hormones studied for their role in metabolic processes.
  • GLP-1 (Glucagon-like peptide-1): A hormone produced in the intestines.
    • Originated in research linked to gastric bypass procedures.
    • Notable for its role in reducing blood glucose levels.

GLP-1 in Endocrinology

  • Traditionally endocrine organs include the thyroid gland, adrenal glands, gonads, etc.
  • Broader Perspective: The brain, heart, muscles, bones, and intestines all produce hormones.
  • GLP-1 is one among many hormones from the intestines leveraged in medications.

GLP-1 Receptor Agonists

  • Function: Increases GLP-1 signaling, leading to decreased glucagon.
  • Effect: Lowered blood glucose levels, ameliorating type 2 diabetes.
  • Initial Use: Low doses were effective in reducing glucagon and controlling diabetes.

Current Uses and Concerns

  • Increased Dosages: Now used in much higher concentrations.
    • Results in slowed gastric emptying.
    • Previously noted as a side effect, now a primary mechanism.
  • Consequences: Risk of intestines paralysis.
    • Can result in severe health issues requiring permanent medical interventions.

Alternative Strategies to Increase GLP-1

  • Dietary Methods:
    • Proteins, certain fats, specific carbohydrates, and fiber can naturally increase GLP-1.
    • Fiber is particularly effective by stimulating L cells in the small intestine.
  • Goal: Promote satiety and fullness with natural methods to avoid drug side effects.

Conclusion

  • Metabolic Advantage: GLP-1 offers significant benefits but must be managed carefully.
  • Risks of Overuse: High dosage GLP-1 agonists can lead to serious gastrointestinal issues.
  • Encouragement: Leverage natural dietary means to enhance GLP-1 for better health outcomes.

Key Takeaway

GLP-1 receptor agonists, while effective for managing diabetes and aiding weight loss, may pose serious risks, including potential permanent paralysis of the intestines.

Summary

  • Dr. Ben Bikman provides a detailed discussion on GLP-1 drugs, which are designed to enhance the action of glucagon-like peptide-1 (GLP-1)—a hormone produced in the intestines.
  • His research dates back to when his dissertation lab was among the first to study incretins, helping lay the groundwork for understanding GLP-1's functions.
  • Originally, GLP-1 receptor agonists were used at lower doses, primarily to manage type 2 diabetes by inhibiting glucagon (which raises blood glucose levels), resulting in lower blood sugar levels as a positive side effect.
  • Over time, the dosages of these medications have been significantly increased, leading to major changes in their effects on the body.
  • One of the primary mechanisms of action of higher GLP-1 doses is the "paralysis of the intestines," which contributes to prolonged gastric emptying and a sense of fullness, but at the risk of detrimental health impacts.
  • In extreme cases, patients have experienced irreversible intestinal paralysis, necessitating alternative nutrition methods such as infusions or colostomy bags.
  • Dr. Bikman emphasizes the balance between the benefits of GLP-1 in managing metabolic processes versus the severe risks of long-term use in higher doses.