Incretins — Advanced Clinical Biochemistry

Biochemistry · Basic Sciences

How it begins

The term "incretin" was coined by La Barre in 1932, but its modern physiological relevance began with the observations of Elrick et al. in 1964 and McIntyre et al. in 1965, who documented that oral administration of glucose produced a significantly greater insulinemic response than the same amount of glucose administered intravenously, despite achieving identical blood glucose levels. This difference…

What it covers

1. The Incretin Effect — Historical and Physiological Foundation
2. · The Two Main Incretins
3. · Reduction of the Incretin Effect in T2DM — 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 Receptors — 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