Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases.
Mosa. Rasha Mofeed Habeeb RM; Zhang. Zhen Z; Shao. Renfu R; Deng. Chao C; Chen. Jiezhong J; Chen. Chen C
Key Findings
- Hexarelin can influence PPARÎł, a key regulator of fat storage and insulin sensitivity, in fat cells and immune cells.
- Ghrelin protects pancreatic beta cells from damage by activating PI3K/Akt, blocking JNK, and keeping FOXO1 out of the nucleus.
- Both acylated and unacylated ghrelin lower glucose levels and increase beta‑cell numbers and insulin release in rodent models.
- These effects suggest possible use of ghrelin/hexarelin for diabetes and related heart disease, independent of growth‑hormone release.
Practical Outcomes
- While the data are promising, they come from cell and animal work, so there’s no safe dosage or protocol for self‑administration yet. Biohackers can keep an eye on upcoming human trials and consider that future supplements might target these pathways, but current use is not recommended without medical supervision.
Summary
The review says that the natural hormone ghrelin and its lab-made cousin hexarelin can help protect and even regrow insulin‑producing cells, lower blood sugar, and improve heart health in animal studies. They work through pathways that boost insulin sensitivity and reduce harmful cell stress, and they may have benefits beyond just raising growth hormone.
Abstract
Ghrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes. PPAR-γ is an important regulator of adipogenesis, lipid metabolism, and insulin sensitization. Ghrelin also shows protective effects on beta cells against lipotoxicity through activation of phosphatidylinositol-3 kinase/protein kinase B, c-Jun N-terminal kinase (JNK) inhibition, and nuclear exclusion of forkhead box protein O1. Acylated ghrelin (AG) and unacylated ghrelin (UAG) administration reduces glucose levels and increases insulin-producing beta cell number, and insulin secretion in pancreatectomized rats and in newborn rats treated with streptozotocin, suggesting a possible role of GHS in pancreatic regeneration. Therefore, the discovery of GHS has opened many new perspectives in endocrine, metabolic, and cardiovascular research areas, suggesting the possible therapeutic application in diabetes and diabetic complications especially diabetic cardiomyopathy. Here, we review the physiological roles of ghrelin and hexarelin in the protection and regeneration of beta cells and their roles in the regulation of insulin release, glucose, and fat metabolism and present their potential therapeutic effects in the treatment of diabetes and diabetic-associated heart diseases.
Study Information
pubmed
2015
2015-02-04T00:00:00.000Z
10.1007/s12020-015-0531-z
18
190