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Key Takeaways
- •Kang, Z. (2012). Impaired Incretin Effects in Type 2 Diabetes: Mechanism and Therapeutic Implication (Doctoral dissertation, Chinese University of Hong Kong).
- •Elliott, R. M., Morgan, L. M., Tredger, J. A., Deacon, S., Wright, J., & Marks, V. (1993). Glucagon-like peptide-1 (7-36) amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. Journal of Endocrinology, 138(1), 159-166.
- •Chang, X., Keller, D., Bjørn, S., & Led, J. J. (2001). Structure and folding of glucagon-like peptide-1-(7-36)-amide in aqueous trifluoroethanol studied by NMR spectroscopy. Magnetic Resonance in Chemistry, 39(8), 477-483.
GLP-1 (7-36) Amide: Incretin Hormone Structure and Role
The proglucagon gene in mammals encodes glucagon along with two related peptides, GLP-1 and GLP-2. This gene exists in both the gut and pancreas. In the pancreas, glucagon represents the primary active product from proglucagon cleavage, while gut processing yields GLP-1 (7-36) amide as the main active peptide, a shortened version of GLP-1. This form dominates in human circulation after meals.
Production and Active Forms
Four GLP-1 variants appear in vivo: inactive GLP-1 (1-37) and GLP-1 (1-36)-NH2, plus active GLP-1 (7-37) and GLP-1 (7-36)-NH2. Enzymes from the PC family convert full precursors into these active types, which equally boost insulin release based on glucose levels. In humans, GLP-1 (7-36)-NH2 prevails in the bloodstream.
Adding an amide group to GLP-1 (1-36) extends the lifespan of GLP-1 (7-36) in plasma. Total GLP-1 levels, covering GLP-1 (7-36)-NH2 and GLP-1 (9-36)-NH2, measure 10-20 pM in fasting plasma of healthy Caucasians. These rise to 30-60 pM within 30 minutes of a 75-g glucose load or mixed meal.
Rapid Degradation Process
Active GLP-1 forms like GLP-1 (7-37) and GLP-1 (7-36)-NH2 break down quickly in vivo into inactive GLP-1 (9-37) and GLP-1 (9-36)-NH2. Dipeptidyl peptidase-4 (DPP-4) cleaves the alanine at position 2, resulting in a half-life below 2 minutes. Check peptide half-lives with our Half-Life Calculator.
Hansen et al. analyzed GLP-1 from porcine ileum and noted that about 75% degrades by DPP-4 before exiting the gut. Studies in anesthetized pigs reveal further liver breakdown, allowing only 10% to 15% of secreted GLP-1 into circulation. Reports indicate less than 5% intact GLP-1 reaches systemic circulation in Japanese individuals.
Molecular Structure Details
GLP-1 (7-36) amide consists of 30 amino acids with sequence HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR-NH2. As an incretin, it enhances glucose-triggered insulin release, promotes insulin production, and suppresses glucagon. These actions position it as a candidate for treating non-insulin-dependent diabetes mellitus, or type II diabetes.
This peptide faces physical instability issues. Its shape, clumping, and dissolving properties vary with purification methods and storage during processing. Detailed studies on its solution structure remain limited, though the alpha-helix stands out as a key feature. GLP-1 forms high-helix oligomers and adopts a helical form in membrane-mimicking dodecylphosphocholine micelles. Beta-sheet structures also matter and contribute to poorly soluble clumps. Use our Stability Calculator and Solubility Predictor for peptide handling insights.
Insulin Stimulation and Broader Effects
GLP-1 (7-36) amide strongly triggers insulin secretion. Alongside glucose-dependent insulinotropic polypeptide (GIP), it functions as an incretin, aiding insulin output through the gut-insulin pathway. Beyond insulin, it mimics insulin's anabolic effects on fat tissue by boosting new fat synthesis and acts as an enterogastrone to block pentagastrin-driven stomach acid production.
Nutrient Responses and Measurement Challenges
GIP secretion triggers from nutrients are well-established. Far less data exists on GLP-1 (7-36) amide blood levels and nutrient impacts. Immunoassay results vary widely, with fasting immunoreactive GLP-1 between 15 pmol/l and 236 pmol/l across studies.
Some research shows modest increases in plasma immunoreactive GLP-1 after oral glucose or mixed meals. Hirota et al. reported a drop in total immunoreactive GLP-1 after oral glucose in healthy people. Variations stem from antibody cross-reactivity with pancreatic GLP-1 forms and inconsistent plasma extraction methods, complicating assignment of clear endocrine roles.
One study developed a radioimmunoassay for human GLP-1 (7-36) amide levels. It assessed short-term responses to various macronutrients, focusing on carbohydrates, alongside GIP. It also tracked GIP and GLP-1 (7-36) amide over 24 hours in healthy subjects on a standard Western diet to mimic everyday eating patterns.
Key Research References
- Kang, Z. (2012). Impaired Incretin Effects in Type 2 Diabetes: Mechanism and Therapeutic Implication (Doctoral dissertation, Chinese University of Hong Kong).
- Elliott, R. M., Morgan, L. M., Tredger, J. A., Deacon, S., Wright, J., & Marks, V. (1993). Glucagon-like peptide-1 (7-36) amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. Journal of Endocrinology, 138(1), 159-166.
- Chang, X., Keller, D., Bjørn, S., & Led, J. J. (2001). Structure and folding of glucagon-like peptide-1-(7-36)-amide in aqueous trifluoroethanol studied by NMR spectroscopy. Magnetic Resonance in Chemistry, 39(8), 477-483.
GLP-1 (7-36) amide holds promise for diabetes management through its incretin actions, despite quick breakdown and stability hurdles. Ongoing research clarifies its secretion patterns and structural traits. Explore more in our Peptide Glossary.