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▎What is HGH 176-191?
hGH Fragment 176-191 is a specific fragment of human growth hormone (hGH), composed of amino acid residues from position 176 to 191 in the hGH molecule.
▎HGH 176-191 Structure
Source: PubChem | Sequence: YLRIVQCRSVEGSCGF Molecular Formula: C78H123N23O22S2 Molecular Weight: 1799.1g/mol CAS Number: 66004-57-7 PubChem CID: 16131230 Synonyms: Somatotropin (176-191) |
▎HGH 176-191 Research
What is the research background of HGH 176-191?
Early research on hGH mainly focused on its role in promoting growth and development. With the deepening of research, scientists found that hGH has a variety of biological functions, and its different structural domains may be responsible for different functions. In order to have a more in-depth understanding of the mechanism of action of hGH, researchers began to pay attention to the functions of its specific fragments. hGH Fragment 176-191 was discovered and studied in such a context. It has been found that this fragment has unique effects in fat metabolism, blood glucose regulation, etc., which provides a new direction for further understanding the physiological functions of hGH and developing related treatment methods.
What is the mechanism of action of HGH 176-191?
1. Mechanism of Action on Breast Cancer Cells
Enhancing Drug Targeting:
Studies have shown that loading hGH Fragment 176-191 and anti-cancer drugs into inert drug carriers (such as chitosan nanoparticles) can enhance the accumulation of tumor drugs in tumor cells. By binding to tumor-related proteins, this fragment can target breast cancer cells, thereby improving the tumor targeting of anti-cancer drugs[1]. For example, in molecular docking simulation experiments, it was found that the hGH Fragment 176-191 peptide can enhance the binding of doxorubicin to multiple breast cancer protein targets, which means that this fragment helps to deliver anti-cancer drugs more precisely to breast cancer cells.
Improving Drug Efficacy:
The hGH Fragment 176-191 peptide can bind to breast cancer receptors, thereby affecting the binding of doxorubicin to these receptors, and further enhancing the anti-cancer efficacy of doxorubicin[1]. In the viability assay of human MCF-7 breast cancer cells, it was confirmed that the dual-loaded chitosan nanoparticles (loaded with hGH Fragment 176-191 peptide and doxorubicin) have stronger anti-proliferative activity against breast cancer cells than chitosan loaded with doxorubicin alone. This dual-loading strategy may improve the anti-cancer efficacy of doxorubicin and reduce the clinical side effects caused by exposure to non-target tissues.
2. Mechanism of Action on Glucose Metabolism
Influencing Glucose Transport:
The synthesized hGH Fragment 176-191 has an effect on glucose transport in adipocytes isolated from genetically obese Zucker rats. This fragment can induce a decrease in basal and insulin-stimulated D[1-14C]-2-deoxyglucose uptake[2]. Compared with the complete human growth hormone molecule, the synthesized hGH Fragment 176-191 peptide is more effective at equimolar concentrations. This indicates that the functional domain of the anti-lipogenic activity of hGH is located in the C-terminal region of the hGH molecule, and the effect on glucose transport may at least partially contribute to the anti-lipogenic properties of the hGH 176-191 peptide as well as the complete hormone.
Regulating Blood Glucose and Insulin Levels:
The synthesized peptide corresponding to human growth hormone amino acids 176-191 can cause a transient increase in blood glucose and a more sustained increase in plasma insulin in normal rats[3]. For example, a single dose (5 nmol/kg body weight) of the peptide containing the amino acid sequence 178-191 of the hGH molecule can significantly reduce the insulin sensitivity of animals in the intravenous insulin tolerance test. This indicates that hGH Fragment 176-191 may exert its biological effects by regulating blood glucose and insulin levels.
Quality of the hGH fragment 176–191 peptide 3D-model structure.
Source:PubMed[1]
What are the applications of HGH 176-191?
1. Enhancing the Efficacy of Antitumor Drugs
As a Targeting Component of Drug Carriers:
Studies have shown that combining HGH 176-191 with chitosan nanoparticles loaded with antitumor drugs such as doxorubicin can enhance the targeting effect of doxorubicin on breast cancer cells[1]. The principle is to increase tumor drug accumulation and local cytotoxicity through inert drug carriers loaded with anti-cancer drugs and peptides that can bind (target) tumor-related proteins. This dual-loading strategy may enhance the anti-cancer efficacy of doxorubicin and reduce the clinical side effects associated with exposure to non-target tissues.
Verification by Molecular Docking Simulation:
Through two sets of computer simulation experiments, namely determining the binding affinity of the HGH 176-191 peptide to breast cancer receptors and the effect of this peptide binding on the binding of doxorubicin to these same receptors, the role of HGH 176-191 in enhancing the anti-cancer efficacy of doxorubicin was confirmed[1]. In addition, photon correlation spectroscopy showed that the synthesized dual-loaded chitosan nanoparticles have clinically favorable particle size, polydispersity index, and zeta potential.
Verification by Cell Experiments:
In the viability assay of human MCF-7 breast cancer cells, the effect of the HGH 176-191 peptide on the anti-cancer efficacy of doxorubicin was further verified. The results showed that the anti-proliferative activity of dual-loaded chitosan nanoparticles against the breast cancer cell line (MCF-7) is greater than that of chitosan loaded with doxorubicin alone[1].
2. Effects on Blood Glucose and Insulin
Influencing Blood Glucose Levels:
The synthesized peptides corresponding to human growth hormone amino acids 172-191, 176-191, 177-191, 178-191, 179-191, and 180-191 were studied in normal rats. It was found that four of these peptides (hGH 172-191, 176-191, 177-191, and 178-191) can cause a transient increase in blood glucose, accompanied by a more sustained increase in plasma insulin[3].
Influencing Insulin Sensitivity:
The peptide containing the amino acid sequence 178-191 of the human growth hormone molecule significantly reduced the insulin sensitivity of animals in the intravenous insulin tolerance test[3]. This indicates that related peptides such as hGH Fragment 176-191 may play a certain role in regulating blood glucose and insulin metabolism.
3. Effects on Adipocyte Metabolism
Anti-lipogenic Effect:
It has been found that the synthesized C-terminal peptide sequence of human growth hormone, hGH 177-191, can induce a decrease in basal and insulin-stimulated D[1-14C]-2-deoxyglucose uptake in adipocytes isolated from genetically obese Zucker rats. Compared with the complete human growth hormone molecule, the synthesized peptide at equimolar concentration is more effective. This indicates that the functional domain of the anti-lipogenic activity of hGH is located in the C-terminal region of the hGH molecule, and the effect on glucose transport may at least partially contribute to the anti-lipogenic properties of the peptide hGH 177-191 as well as the complete hormone[2, 4].
Main Effect on Lipid Metabolism:
Studies on the synthesized C-terminal peptide fragment of human growth hormone, hGH 177-191, have shown that it has the same anti-lipogenic activity as the complete human growth hormone molecule, and by measuring the glycerol release rate in the epididymal fat pads of peptide-treated rats, no obvious lipolytic effect of hGH 177-191 was found. This supports the view that the main physiological role of human growth hormone in lipid metabolism lies at the level of lipogenesis, and the functional domain of the anti-lipogenic activity of hGH is located in the C-terminal region of the molecule[4].
In which disease areas may HGH 176-191 (hGH 176-191) be useful?
Patients with Obesity and Related Metabolic Disorders:
hGH Fragment 176-191 can promote fat breakdown and increase the oxidative utilization of fatty acids, thus helping to reduce fat accumulation in the body. For obese patients, it can help reduce body weight and improve a series of metabolic disorders caused by obesity, such as insulin resistance and dyslipidemia.
Patients with Type 2 Diabetes Mellitus:
On the one hand, it can improve the insulin sensitivity of adipocytes by promoting fat metabolism and reducing lipid accumulation in adipocytes, enabling insulin to function better and reducing blood glucose levels. On the other hand, this fragment may also have a certain protective effect on pancreatic islet β cells, helping to maintain the function of pancreatic islet β cells and promoting the normal secretion of insulin.
Patients at High Risk of Cardiovascular Diseases:
Since hGH Fragment 176-191 can regulate fat metabolism, reduce the levels of atherogenic lipids such as triglycerides and low-density lipoprotein cholesterol in the blood, and increase the content of high-density lipoprotein cholesterol, it can help reduce the degree of atherosclerosis and lower the risk of cardiovascular diseases. For patients with high-risk factors for cardiovascular diseases, such as obesity, hyperlipidemia, and hypertension, it may have a certain cardiovascular protective effect.
In conclusion, hGH Fragment 176-191 can reduce the glucose uptake of adipocytes and has anti-lipogenic activity in regulating adipocyte metabolism; it shows effects such as a transient increase in blood glucose, a sustained increase in insulin, and a decrease in insulin sensitivity in blood glucose regulation; in the field of tumor treatment, it can enhance the anti-cancer efficacy of doxorubicin against breast cancer cells. Its diverse effects provide new directions for the research and treatment of diseases such as obesity, diabetes, and breast cancer.
About The Author
The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.
Scientific Journal Author
Habibullah M M is an accomplished academic and researcher affiliated with prestigious institutions such as Jazan University, Najran University, and the University of Sheffield. His research interests span a wide range of disciplines, including pharmacology and pharmacy, general and internal medicine, biochemistry and molecular biology, health care sciences and services, and interdisciplinary topics in science and technology. With a focus on advancing knowledge in these fields, his work contributes significantly to both theoretical and applied research, addressing critical challenges in health care and scientific innovation. Habibullah M M is listed in the reference of citation [1].
▎Relevant Citations
[1] Habibullah M M, Mohan S, Syed N K, et al. Human Growth Hormone Fragment 176-191 Peptide Enhances the Toxicity of Doxorubicin-Loaded Chitosan Nanoparticles Against MCF-7 Breast Cancer Cells[J]. Drug Des Devel Ther, 2022,16:1963-1974.DOI:10.2147/DDDT.S367586.
[2] Wijaya E, Ng F M. Effect of an antilipogenic fragment of human growth hormone on glucose transport in rat adipocytes[J]. Biochem Mol Biol Int, 1993,31(3):543-552.https://pubmed.ncbi.nlm.nih.gov/8118430/
[3] Ng F M, Bornstein J. Hyperglycemic action of synthetic C-terminal fragments of human growth hormone[J]. Am J Physiol, 1978,234(5):E521-E526.DOI:10.1152/ajpendo.1978.234.5.E521.
[4] Wu Z, Ng F M. Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone.[J]. Biochemistry and Molecular Biology International, 1993,30 1:187-196. https://pubmed.ncbi.nlm.nih.gov/8358331/
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