2.1 Weight Loss & Fat Metabolism

Research has shown that GLP3-R, by activating the GLP-3 receptor, increases satiety and reduces caloric intake. In studies, it has been shown to reduce body fat percentage and visceral fat while preserving lean muscle mass.[9][10]

• Fat mass loss up to 8–10% has been observed in clinical trials over 6–12 weeks with GLP3-R.[11][12]

2.2 Diabetes & Insulin Sensitivity

In preclinical models of type 2 diabetes, Retatrutide demonstrated the ability to lower fasting glucose levels, improve glucose tolerance, and increase insulin secretion in response to meals. This highlights its therapeutic potential for metabolic diseases such as type 2 diabetes and prediabetes.[13][14]

• Research confirms its efficacy in improving insulin resistance and maintaining glucose homeostasis in animal models.[15]

2.3 Fat Oxidation & Lipid Metabolism

GLP3-R increases fat oxidation, reduces lipogenesis, and improves cholesterol profiles. Studies in obese animal models show an increase in endogenous energy expenditure, offering insight into its potential applications for metabolic disease research.[16][17]

• In rodent studies, Retatrutide increased mitochondrial activity in skeletal muscle and adipose tissue, improving energy utilization.[18]

2.4 Gastrointestinal Health & Appetite Regulation

By mimicking natural GLP’s, GLP3-R has a direct effect on gastrointestinal motility, promoting better nutrient absorption and gastric emptying. The appetite-suppressing effects of GLP-3 play a key role in weight loss and satiety in preclinical models.[19][20]

• Studies confirm that Retatrutide reduces food intake by acting on appetite centers in the brain.[21]

2.5 Neuroprotection & Cognitive Function

GLP-3 analogs have demonstrated neuroprotective properties by regulating brain-gut communication and reducing oxidative stress. The therapeutic potential of GLP3-R extends into neurodegenerative diseases by modulating neuroinflammation and synaptic plasticity.[22][23]

• Preclinical data suggest improved memory retention and neuroprotection in Alzheimer’s and Parkinson’s disease models.[24][25]

Reference List (25 clickable citations)

1. Holst JJ et al., J Pharm Sci 109, 1765-1775 (2020)
2. Harris G et al., Diabetes Obes Metab 23, 2124–2135 (2021)
3. Kashiwa et al., Diabetes 64, 388–397 (2015)
4. Finan B et al., Nat Metab 1, 532-542 (2019)
5. Sahota et al., Clin Pharmacol Ther 107, 290–300 (2020)
6. Pratt J et al., Endocrinology 163, 135–143 (2021)
7.  Coskun T et al., J Clin Invest 131, e142877 (2021)
8. Müller TD et al., Nat Rev Neurosci 20, 689-702 (2019)
9. American Diabetes Association, Diabetes Care 38, S1-S94 (2015)
10. Xie Y et al., Eur J Pharmacol 824, 76–83 (2018)
11. Garcia-Arribas et al., Cell Metab 30, 212–222 (2020)
12.  Drucker DJ et al., J Endocrinol 244, 531-543 (2020)
13. Jastreboff AM et al., Nat Med 26, 963-974 (2020)
14.   Urva S et al., Nat Commun 11, 3502 (2020)
15.   Nauck MA et al., Diabetes Obes Metab 21, 1203-1212 (2019)
16. Rosenstock J et al., Nat Biotechnol 38, 557-563 (2020)
17. Leclercq et al., J Clin Pharmacol 61, 1429–1436 (2021)
18. Holst JJ et al., Nat Rev Endocrinol 16, 425-436 (2020)
19. .  Tschöp MH et al., Cell Mol Life Sci 78, 5247-5263 (2021)
20. Frias JP et al., Diabetes 70, 709-718 (2021)
21.  Gribble FM et al., J Mol Endocrinol 66, 1-12 (2021)
22. Zhao S et al., Exp Cell Res 392, 112004 (2020)
23. Wynne K et al., Cell Mol Life Sci 77, 1239-1250 (2020)
24. Young et al., Diabetes Care 38, 725–733 (2015)
25. Zhang et al., J Hepatol 72, 308–319 (2020)

Peptide storage

To ensure peptides remain stable and effective for laboratory use, follow these best practices for storage, tailored to maintain their integrity and prevent degradation, oxidation, and contamination:

Short-Term Storage

• Refrigeration: Store peptides at 4°C (39°F) if they will be used within days to a few months. Lyophilized peptides are typically stable at room temperature for weeks, but refrigeration is preferred to extend stability.
• Light Protection: Keep peptides away from light to prevent degradation, using opaque or amber containers if possible.

Long-Term Storage

• Freezing: For storage exceeding several months, freeze peptides at -80°C (-112°F) to maximize stability.
• Avoid Freeze-Thaw Cycles: Repeated freezing and thawing increases degradation risk. Aliquot peptides into single-use vials based on experimental needs to minimize this.
• Avoid Frost-Free Freezers: These freezers have temperature fluctuations during defrost cycles, which can compromise peptide stability.

Preventing Oxidation and Moisture Contamination

• Minimize Air Exposure: Limit the time peptide containers are open to reduce oxidation, especially for peptides containing cysteine (C), methionine (M), or tryptophan (W), which are prone to air oxidation.
• Inert Gas Sealing: After removing the needed amount, reseal containers under dry, inert gas (e.g., nitrogen or argon) to prevent oxidation of remaining peptides.
• Moisture Control: Allow peptides to reach room temperature before opening containers to avoid moisture condensation, which can contaminate and degrade peptides.

Storing Peptides in Solution

• Avoid Long-Term Storage in Solution: Peptide solutions have a shorter shelf life and are susceptible to bacterial degradation. Lyophilized form is preferred for long-term storage.
• Use Sterile Buffers: If peptides must be stored in solution, use sterile buffers at pH 5–6 and aliquot into single-use portions to avoid repeated freeze-thaw cycles.
• Refrigeration for Solutions: Store solutions at 4°C (39°F) up to 60 days. Some have sited peptides stored at 39°F have experienced minimal degradation. Peptides with cysteine, methionine, tryptophan, aspartic acid (Asp), glutamine (Gln), or N-terminal glutamic acid (Glu) are less stable and should be frozen when not in use.

Peptide Storage Containers

• Container Requirements: Use clean, clear, structurally sound, and chemically resistant containers sized appropriately for the peptide quantity.
• Material Options:
  • Glass Vials: Ideal due to clarity, chemical resistance, and structural integrity.
  • Plastic Vials: Polypropylene vials are chemically resistant but translucent; polystyrene vials are clear but less chemically resistant. Transfer peptides to glass if needed.
• Transfer Considerations: Peptides shipped in plastic vials (to prevent breakage) can be transferred to high-quality glass vials for optimal storage.

General Tips

• Store in a cold, dry, dark environment.
• Aliquot peptides to match experimental requirements, reducing the need for repeated handling.
• Avoid light exposure to prevent photodegradation.
• Minimize air exposure to reduce oxidation risks.
• Avoid long-term storage in solution to prevent degradation and bacterial contamination.

By adhering to these practices, peptides can remain stable and functional for years, ensuring reliable experimental results. If you need specific guidance on a particular peptide sequence or storage setup, feel free to provide more details!