Pancragen Peptide: Cellular, Metabolic, and Pancreatic Implications

Pancragen is a tetrapeptide composed of the amino acid sequence Lys-Glu-Asp-Trp (KEDW).⁽¹⁾ It is a synthetic analog derived from a peptide originally isolated from bovine pancreatic cells and has been identified as a potential peptide bioregulator with implications for pancreatic function and age-associated metabolic processes.

Pancragen has garnered attention for its potential to influence pancreatic function by possibly regulating key cellular activities. Distinct from the DNA-based PancraGEN test, Pancragen peptide is speculated to be associated with the regulation of pancreatic function. These functions are thought to include blood sugar control, endocrine function support, and the modulation of metabolic syndrome factors.

Overview

Research suggests that Pancragen may penetrate cellular membranes and interact with nuclear components, potentially influencing gene transcription and promoting cell differentiation within the pancreas. This interaction is thought to up-regulate critical differentiation factors such as Ptf1a, Pdx1, Pax6, Foxa2, Nkx2.2, and Pax4, which are essential for the maturation of pancreatic cells.⁽²⁾ Pancragen may support the expression of functional molecules, including MMP2, MMP9, and serotonin, indicating a possible increase in pancreatic cell activity.

Moreover, Pancragen might influence apoptosis-related proteins by reducing the expression of the proapoptotic protein p53 and increasing the antiapoptotic protein Mcl1, suggesting an antiapoptotic potential. The peptide may also modulate cellular aging biomarkers by reducing the activities of caspase-3 and cathepsin B, as well as adjusting levels of TNF-α and IGF-I, which are associated with metabolic regulation and antiapoptotic actions. Additionally, Pancragen may alter the methylation patterns of genes like PDX1, PAX6, and NGN3, possibly contributing to its potential anti-aging impact on pancreatic cells.

 

Research

Pancragen Peptide and Metabolic Dysregulation

Investigations into Pancragen’s potential impacts on metabolic dysregulation in test models have yielded insights into its possible influence on carbohydrate metabolism.

In one study, the primary focus was on the peptide’s role in modulating glucose homeostasis. The introduction of Pancragen was associated with a significant reduction in fasting glucose levels during a standard glucose tolerance test, accompanied by decreased insulin concentrations and a lower insulin resistance index. These findings suggest that Pancragen may have a role in mitigating disturbances in carbohydrate metabolism, particularly given the observed persistence of its glucose-lowering impacts following cessation of exposure.

It is important to recognize that this study was conducted on test models, and several variables, including the severity of insulin resistance and other metabolic factors, may influence the scope of Pancragen’s impacts. Researchers noted that the introduction of tetrapeptides appears to be “a promising approach to the correction of insulin resistance in subjects.”

Another study sought to examine the potential impact of Pancragen on the endocrine function of pancreatic cells and the metabolic status of test models.⁽⁴⁾ The research aimed to explore Pancragen’s potential in addressing cellular age-related dysfunctions in overall metabolism and the pancreatic islet apparatus. In test models, a reduced rate of glucose utilization was observed compared to younger counterparts, alongside elevated insulin and C-peptide peaks at 5- and 15-minutes post-glucose introduction.

Researchers observed that the daily introduction of Pancragen over 10 days resulted in notable support in glucose utilization rates. This intervention also appeared to normalize the dynamics of plasma insulin and C-peptide responses to glucose. Interestingly, the impacts of Pancragen persisted, with some additional support for metabolic status and pancreatic cell function remained observable to researchers three weeks after the trial concluded.

In a separate study investigating the impacts of Pancragen on endothelial function under conditions of chronic hyperglycemia using murine models,⁽⁵⁾ the peptide was observed to restore endothelial adhesive properties potentially. The restoration of these adhesive characteristics is considered to be critical, as proper endothelial function is essential for maintaining blood flow regulation and mitigating complications such as atherosclerosis in models of metabolic dysregulation.

Deficiencies or abnormalities in endothelial adhesion may increase susceptibility to vascular damage, underscoring the significance of this restoration as a target for mitigating such risks. At the conclusion of this study, researchers noted that the results “indicate homeostatic and endothelioprotective impacts of pancragen during the early period of diabetes mellitus.”

Pancragen Peptide and Pancreatic Function

Pancragen has been explored for its potential impacts on pancreatic cellular processes, particularly cell differentiation and the regulation of insulin and glucagon secretion, which are critical to the pancreas’s endocrine function.

Research indicates that Pancragen may be capable of penetrating cellular membranes and interacting with nuclear components, potentially influencing the transcription of genes that are essential for the differentiation of pancreatic cells. Specifically, key transcription factors such as Ptf1a, Pdx1, Pax6, Foxa2, Nkx2.2, and Pax4 are integral to the development and function of various pancreatic cell types. It is hypothesized that Pancragen may up-regulate the expression of these factors, thereby facilitating the maturation process of acinar and islet cells.

Experimental data from studies involving embryonic cultures of pancreatic acinar cells suggest that Pancragen might support the expression of Ptf1a and Pdx1, proteins vital for the maturation of these cells. Notably, these impacts appear to be more pronounced in certain older cultures, where a decline in the expression of these proteins is typically observed as part of the cellular aging process. By potentially up-regulating these critical differentiation factors, Pancragen may contribute to the increased differentiation of pancreatic cells, potentially restoring their functional activity to levels more characteristic of younger cell cultures.

In another study⁽⁶⁾ utilizing murine models, the impacts of Pancragen on the functional morphology of the pancreas were investigated. When diabetes mellitus (DM) was induced in these models, there was a notable decrease in insulin-producing β cells and an increase in glucagon-producing α cells, indicating disrupted pancreatic function.

Researchers overseeing test models in a laboratory setting observed that, following exposure to Pancragen, the test models exhibited compensatory changes within pancreatic cells and tissue. Specifically, there was an observable increase in support for insulin production by β cells and a reduction in glucagon production by α cells. Additionally, the proliferative activity of certain pancreatic cells and their apoptotic rates appeared to normalize, aligning more closely with those observed in control models.

Further research suggests that Pancragen may play a significant role in modulating various cellular markers and proteins associated with the vitality of pancreatic cells.⁽⁷⁾ In pancreatic cell cultures, Pancragen exposure was associated with increased expression of matrix metalloproteinases MMP2 and MMP9, serotonin, glycoprotein CD79alpha, the antiapoptotic protein Mcl1, and proliferation markers PCNA and Ki67. Concurrently, a reduction in the expression of the proapoptotic protein p53 was observed. These findings imply that Pancragen may activate signaling molecules that serve as markers of the functional activity of pancreatic cells, suggesting its potential role in maintaining or restoring pancreatic cell function.

Pancragen Peptide and Cellular Aging

To assess its impacts on cellular aging, a study⁽⁸⁾ explored the impact of Pancragen on murine models across different age groups. The study reported a decrease in specific cellular aging biomarkers, such as caspase-3 and cathepsin B activities, following Pancragen exposure in younger murine models. Notably, in mature models, Pancragen implication led to a significant reduction in TNF-α levels and an increase in IGF-I, both of which are critical markers associated with cellular aging and metabolic regulation.

Additionally, in a rapid experimental cellular aging model induced by diabetes mellitus, Pancragen appeared to normalize blood glucose levels, reinforcing its previously suggested hypoglycemic properties. The study also observed that Pancragen might suppress certain apoptotic enzymes within pancreatic cells, indicating that its biological actions may be linked to both metabolic regulation and antiapoptotic mechanisms. The influence of Pancragen on endogenous cellular aging might be mediated through its impacts on IGF-I, a well-studied “survival factor” with antiapoptotic properties. Moreover, Pancragen’s potential interaction with specific genes suggests that its impact may extend to proteolytic processing pathways.

Another study⁽⁹⁾ examined the tissue-specific impacts of Pancragen on gene expression in pancreatic cell cultures. The research indicated that alterations in the methylation patterns of the PDX1, PAX6, and NGN3 gene promoter regions in pancreatic cells may be associated with cellular aging and might contribute to changes in gene expression levels. These findings suggest that modifications in promoter methylation patterns may drive long-term changes in gene expression during cellular aging. Interestingly, the expression levels of the PAX4 and FOXA2 genes in pancreatic cells appeared to diverge with cellular aging and in response to Pancragen, even when the methylation patterns of the PAX4 gene remained consistent.

Notably, the FOXA2 gene promoter region in pancreatic cells displayed only a few methylated CpG sites, with methylation levels influenced by both cell culture aging and Pancragen exposure. However, these changes did not correlate directly with variations in gene expression levels. This suggests that while Pancragen may influence certain gene methylation patterns, the relationship between methylation and gene expression is complex and potentially regulated by additional, unidentified mechanisms.

Pancragen Peptide and Cellular Protection

Pancragen has been suggested to play a protective role against cellular stress and damage, potentially due to its antioxidant properties. It is hypothesized that Pancragen may mitigate oxidative stress by scavenging free radicals or by supporting endogenous antioxidant defenses. Additionally, Pancragen may modulate inflammatory responses by downregulating pro-inflammatory cytokines and promoting the expression of anti-inflammatory mediators. These protective mechanisms may contribute to the preservation of cellular integrity under stress conditions, potentially mitigating potential harm to cellular function in environments of heightened oxidative or inflammatory stress.

 
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References:

1. Goncharova ND, Ivanova LG, Oganian TÉ, Vengerin AA, Khavinson VKh. [Impact of tetrapeptide package on the endocrine function of the pancreas in old monkeys]. Adv Gerontol. 2014;27(4):662-7. Russian. PMID: 25946840. https://pubmed.ncbi.nlm.nih.gov/25946840/
2. Khavinson, V. K.h, Durnova, A. O., Polyakova, V. O., Tolibova, G. H., Linkova, N. S., Kvetnoy, I. M., Kvetnaia, T. V., & Tarnovskaya, S. I. (2013). Impacts of pancragen on the differentiation of pancreatic cells during their aging. Bulletin of experimental biology and medicine, 154(4), 501–504. https://doi.org/10.1007/s10517-013-1987-6
3. Korkushko, O. V., Khavinson, V. K.h, Shatilo, V. B., Antonyk-Sheglova, I. A., & Bondarenko, E. V. (2011). Prospects of using pancragen for correction of metabolic disorders in elderly people. Bulletin of experimental biology and medicine, 151(4), 454–456. https://doi.org/10.1007/s10517-011-1354-4
4. Anisimov VN, Khavinson VKh. Peptide bioregulation of aging: results and prospects. Biogerontology. 2010 Apr;11(2):139-49. doi: 10.1007/s10522-009-9249-8. Epub 2009 Oct 15. PMID: 19830585. https://pubmed.ncbi.nlm.nih.gov/19830585/
5. Khavinson, V. K.h, Gavrisheva, N. A., Malinin, V. V., Chefu, S. G., & Trofimov, E. L. (2007). Impact of pancragen on blood glucose level, capillary permeability and adhesion in rats with experimental diabetes mellitus. Bulletin of experimental biology and medicine, 144(4), 559–562. https://doi.org/10.1007/s10517-007-0377-3
6. Kvetnoi, I. M., Ryzhak, A. P., Kostyuchek, I. N., & Tafeev, Y. A. (2007). Impact of tetrapeptide pancragene on functional morphology of the pancreas in rats with experimental diabetes mellitus. Bulletin of experimental biology and medicine, 143(3), 368–371. https://doi.org/10.1007/s10517-007-0114-y
7. Khavinson, V. K.h, Sevost’ianova, N. N., Durnova, A. O., Lin’kova, N. S., Tarnovskaia, S. I., Dudkov, A. V., & Kvetnaia, T. V. (2012). Advances in gerontology = Uspekhi gerontologii, 25(4), 680–684.
8. Khavinson, V. K.h, Gapparov, M. M., Sharanova, N. E., Vasilyev, A. V., & Ryzhak, G. A. (2010). Study of biological activity of Lys-Glu-Asp-Trp-NH2 endogenous tetrapeptide. Bulletin of experimental biology and medicine, 149(3), 351–353. https://doi.org/10.1007/s10517-010-0944-x
9. Ashapkin, V. V., Linkova, N. S., Khavinson, V. K.h, & Vanyushin, B. F. (2015). Epigenetic mechanisms of peptidergic regulation of gene expression during aging of human cells. Biochemistry. Biokhimiia, 80(3), 310–322. https://doi.org/10.1134/S0006297915030062