Incretins — Advanced Clinical Biochemistry

Biochemistry · Basic Sciences

How it begins

El término "incretina" fue acuñado por La Barre en 1932, pero su relevancia fisiológica moderna comenzó con las observaciones de Elrick et al. en 1964 y McIntyre et al. en 1965, quienes documentaron que la administración oral de glucosa producía una respuesta insulinémica significativamente mayor que la misma cantidad de glucosa administrada vía intravenosa, a pesar de alcanzar idénticas glucemias. Esta diferencia…

What it covers

1. The Incretin Effect — Historical and Physiological Foundation
2. · The Two Main Incretins
3. · Reduction of the Incretin Effect in DM2 — Mechanisms
4. GLP-1 — Synthesis, Structure and Systemic Biology
5. · The Proglucagon Gene and Differential Processing
6. · Molecular Structure of Active GLP-1
7. · Biological Actions of GLP-1 — Multiorgan Effects
8. GIP — Biology, K Cells and Resistance in Obesity
9. · Synthesis and Secretion by the K Cell
10. · GIP actions
11. Other Incretin and Related Peptides
12. GLP-1R and GIPR Receivers — Structure and Distribution
13. · Ligand-Receptor Binding Mechanism (Two-Domain Model)
14. Intracellular Signaling Cascades
15. · The Canonical Pathway: Gαs → Adenylate Cyclase → cAMP
16. · Biased Signaling — GLP-1R and β-Arrestins
17. · Regulation of the Circadian Clock by Incretins
18. DPP-4 — The Limiting Enzyme and Its Multiple Faces
19. · Structure and Location
20. · Relevant Physiological Substrates of DPP-4
21. GLP-1R agonists — From Exenatide to Semaglutide
22. · Structural Strategies to Resist Degradation by DPP-4
23. DPP-4 inhibitors — Gliptins
24. Tirzepatide and the Horizon of Polyagonists
25. · Tirzepatide — Molecular Design and Mechanism
26. · GLP-1/GIP/GCG Polyagonists — The Triple Jump
27. Cardiovascular Trials — MACE and Beyond
28. Obesity, MASH and Nephroprotection
29. · GLP-1 RA in Obesity — More than Antidiabetics
30. · MASH (Metabolic Dysfunction-Associated Steatohepatitis)
31. · GLP-1 RA and Nephroprotection — FLOW Trial
32. CNS, Neuroprotection and Addiction
33. · GLP-1 and Alzheimer's Disease / Neurodegeneration
34. · GLP-1R and the Reward System — Implications in Addictions
35. Safety and Adverse Effects
36. · GLP-1 RA — Adverse Effects Profile
37. Integrated Summary — Clinical Biochemistry of Incretins
38. · Current Therapeutic Positioning (ADA/EASD Guidelines 2024)
39. · Mechanistic Comparison: GLP-1 RA vs iDPP-4
40. · Summary of Fundamental Biochemical Keys