Peptides and Osteoporosis: GLP-1 Studies

New bone is always being formed, and old bone is continually broken down, known as bone rejuvenation. A bone mass grows throughout the early stages of life because the organism creates new bone faster than it breaks down existing bone.

The risk of developing osteoporosis (OP) is influenced, in part, by the amount of bone mass achieved in the early stages of life. A greater peak bone mass is associated with a lower risk of osteoporosis over time because more bone is "in the bank."

Conversely, calcium accounts for 1.5 to 2% of total weight, making it the most abundant mineral in the organism. Bones contain about 99% of the calcium an organism has. Preventing osteoporosis is one of the many reasons why calcium is so important.

As suggested in earlier research, walnut protein hydrolysate (WPH) has several bioactivities, including immunological regulatory effects, anti-oxidation, anti-tumor, angiotensin-converting enzyme inhibition, and hypolipidemic properties. This led scientists to look at how WPH affected OP.

The WPH was made by simulating the digestive process. They studied WPH's relative molecular weight distribution, amino acid content, and degree of hydrolysis (DH). With a relative average molecular weight of 572 and a DH of 11.6%, WPH was abundant in Glu and Pro. Using a rat model of retinoic acid-induced OP, the pharmacological impact of WPH on OP was extensively studied.

Finally, WPH has been hypothesized to protect against retinoic acid-induced OP because it may improve bone microstructure, promote bone production, and regulate serum bone metabolism markers. Among the fifteen peptides isolated from WPH, their amino acid sequences matched those of substances with a high potential to bind calcium. This research provides valuable information for developing walnut protein products with added value. It raises the prospect of using WPH as a functional food component in the context of OP.

By binding to bitter taste receptors, an exopolysaccharide preparation of Bacillus amyloliquefaciens triggers the production of glucagon-like peptide 1.

Microbes, including bacteria, fungi, and algae, can secret microbial exopolysaccharides (EPS). Some have speculated that they might have many uses in research. As an example, the Gram-positive bacteria Bacillus amyloliquefaciens may have several potential uses, including as a probiotic in various animal models, a means of regulating host metabolism, a means of protecting mice from obesity caused by a high-fat diet , and as an aid in insulin secretion and type 2 diabetes symptoms. In addition, in vitro studies have purported that the EPS preparation of Bacillus amyloliquefaciens amy-1 may regulate glycemic levels and promote the production of glucagon-like peptide 1 (GLP-1).

Research suggests that intestinal L-cells may release the peptide GLP-1 after a meal. GLP-1 seems to have several physiological impacts, such as increasing insulin production in response to glucose, improving the proliferation and survival of β-cells, blocking glucagon release, and  gastric emptying and food intake.

GLP-1 Peptide Research

The goal of this study by researchers at the National Pingtung University of Science and Technology was to determine how EPS may trigger the release of GLP-1.

Bitter taste receptors (TAS2Rs or T2Rs) are members of the superfamily of seven-transmembrane G protein-coupled receptors; more than half of the substances researched in laboratories globally target these receptors, which is why PES is bitter in solution. The canonical location of T2Rs is in the taste buds, which are responsible for initiating the sense of bitter taste.

The activation of phospholipase C isoform β2 (PLCβ2) by the released Gβγ-complex triggers the production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). The IP3 receptor (IP3R) is an intracellular ion channel that permits the release of Ca2+ from the intracellular endoplasmic reticulum (ER store). Transient receptor potential channel subfamily M member 4 and 5 (TRPM4/5) complexes are plasma membrane-localized sodium-selective channels that, when activated, cause depolarization and, subsequently, the activation of voltage-gated sodium channels (VGSC) in response to an increase in intracellular Ca2+.

According to Ahmad et al., the neurotransmitter ATP is released when the complex of pannexin1 channels and calcium homeostasis modulator 1 and 3 (CALHM1/3) channels is activated by a combination of elevated Ca2+ and membrane depolarization. The discharge of neurotransmitters produces a feeling of bitterness. At the same time, the intracellular concentration of cAMP is reduced because the Gα-gustducin subunit is released and activated by a phosphodiesterase, which then transforms it into AMP.

Inhibitors of the G protein-coupled receptor pathway inhibited the response that EPS caused a concentration-dependent calcium response from the NCI-H716 enteroendocrine cell line. EPS stimulated T2R14 and T2R38, which were produced heterologously (PAV). Data suggests that T2R14 is involved in the effects speculated in NCI-H716 cells since the shRNAs of T2R14 appeared to successfully suppress the EPS-induced calcium response and GLP-1 secretion. The role of T2R38 was not investigated since it is expressed by NCI-H716 cells (AVI).

GLP-1 for sale is available at Core Peptides for researchers interested in further studying this compound.

References

[i] Sung, Wei-Wen, et al. "Bacillus amyloliquefaciens exopolysaccharide preparation induces glucagon-like peptide 1 secretion through the activation of bitter taste receptors." International Journal of Biological Macromolecules (2021).

[ii] Trujillo JM, Nuffer W, Smith BA. GLP-1 receptor agonists: an updated review of head-to-head clinical studies. Ther Adv Endocrinol Metab. 2021 Mar 9;12:2042018821997320. doi: 10.1177/2042018821997320 . PMID: 33767808; PMCID: PMC7953228.

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[iv] Haq Ansari HU, Qazi SU, Sajid F, Altaf Z, Ghazanfar S, Naveed N, Ashfaq AS, Siddiqui AH, Iqbal H, Qazi S. Efficacy and safety of glucagon-like-peptide-1 receptor agonists on body weight and cardiometabolic parameters in individuals with obesity and without diabetes: A systematic review and meta-analysis. Endocr Pract. 2023 Nov 27:S1530-891X(23)00758-9. doi: 10.1016/j.eprac.2023.11.007 . Epub ahead of print. PMID: 38029929.

[v] Zhao X, Wang M, Wen Z, Lu Z, Cui L, Fu C, Xue H, Liu Y, Zhang Y. GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects. Front Endocrinol (Lausanne). 2021 Aug 23;12:721135. doi: 10.3389/fendo.2021.721135 . PMID: 34497589; PMCID: PMC8419463.