Abstract:BACKGROUND AND OBJECTIVE: Considering the association between colorectal cancer (CRC) and both insulin resistance and obesity, and the prominent role of ghrelin in these metabolic disorders, we explored whether plasma levels of ghrelin were associated with CRC. Moreover, in the patients with CRC the possible correlations between ghrelin and insulin, insulin resistance, and body mass index (BMI) as an indicator of obesity were examined. METHODS: A total of 170 subjects, including 82 cases with CRC and 88 con… Show more
“…Correspondingly, in vivo experiments with intestinal carcinogenesis mouse models have demonstrated that ghrelin might decrease the occurrence of inflammation-related colon cancer [104]. Recent research further highlights a correlation between low plasma ghrelin levels, obesity, insulin resistance, and increased vulnerability to colon cancer [105].…”
This review elucidates the critical role of ghrelin, a peptide hormone mainly synthesized in the stomach in various gastrointestinal (GI) diseases. Ghrelin participates in diverse biological functions ranging from appetite regulation to impacting autophagy and apoptosis. In sepsis, it reduces intestinal barrier damage by inhibiting inflammatory responses, enhancing GI blood flow, and modulating cellular processes like autophagy and apoptosis. Notably, in inflammatory bowel disease (IBD), serum ghrelin levels serve as markers for distinguishing between active and remission phases, underscoring its potential in IBD treatment. In gastric cancer, ghrelin acts as an early risk marker, and due to its significant role in increasing the proliferation and migration of gastric cancer cells, the ghrelin–GHS-R axis is poised to become a target for gastric cancer treatment. The role of ghrelin in colorectal cancer (CRC) remains controversial; however, ghrelin analogs have demonstrated substantial benefits in treating cachexia associated with CRC, highlighting the therapeutic potential of ghrelin. Nonetheless, the complex interplay between ghrelin’s protective and potential tumorigenic effects necessitates a cautious approach to its therapeutic application. In post-GI surgery scenarios, ghrelin and its analogs could be instrumental in enhancing recovery and reducing complications. This article accentuates ghrelin’s multifunctionality, shedding light on its influence on disease mechanisms, including inflammatory responses and cancer progression, and examines its therapeutic potential in GI surgeries and disorders, advocating for continued research in this evolving field.
“…Correspondingly, in vivo experiments with intestinal carcinogenesis mouse models have demonstrated that ghrelin might decrease the occurrence of inflammation-related colon cancer [104]. Recent research further highlights a correlation between low plasma ghrelin levels, obesity, insulin resistance, and increased vulnerability to colon cancer [105].…”
This review elucidates the critical role of ghrelin, a peptide hormone mainly synthesized in the stomach in various gastrointestinal (GI) diseases. Ghrelin participates in diverse biological functions ranging from appetite regulation to impacting autophagy and apoptosis. In sepsis, it reduces intestinal barrier damage by inhibiting inflammatory responses, enhancing GI blood flow, and modulating cellular processes like autophagy and apoptosis. Notably, in inflammatory bowel disease (IBD), serum ghrelin levels serve as markers for distinguishing between active and remission phases, underscoring its potential in IBD treatment. In gastric cancer, ghrelin acts as an early risk marker, and due to its significant role in increasing the proliferation and migration of gastric cancer cells, the ghrelin–GHS-R axis is poised to become a target for gastric cancer treatment. The role of ghrelin in colorectal cancer (CRC) remains controversial; however, ghrelin analogs have demonstrated substantial benefits in treating cachexia associated with CRC, highlighting the therapeutic potential of ghrelin. Nonetheless, the complex interplay between ghrelin’s protective and potential tumorigenic effects necessitates a cautious approach to its therapeutic application. In post-GI surgery scenarios, ghrelin and its analogs could be instrumental in enhancing recovery and reducing complications. This article accentuates ghrelin’s multifunctionality, shedding light on its influence on disease mechanisms, including inflammatory responses and cancer progression, and examines its therapeutic potential in GI surgeries and disorders, advocating for continued research in this evolving field.
“…After about twelve to fourteen hours overnight fasting of 170 subjects, the blood samples were obtained in EDTA (anticoagulant), inside microtubes. The samples at 4°C were centrifuged and immediately the plasma was separated and kept at -80°C (24). The plasma level in form of unit of ng/ml of insulin and adiponectin were calculated by Enzyme-linked immunosorbent assay (ELISA) kit (Mercodia, Sweden, and Technique, Finlanl, respectively).…”
Background: Despite clinical and basic different investigations, the role of plasma adipokines, such as adiponectin as a precise predictor of the risk of colorectal cancer (CRC) is still conflicting.
Aim: This study investigated the association between CRC and insulin resistance, obesity, and plasma adiponectin level for the first time in Iran.
Method: A total of 80 subjects (including 45 CRC patients and 35 healthy individuals) were enrolled in this case-control study. Demographic, anthropometric, and clinical data were recorded, and serum levels of adiponectin, insulin, and glucose were evaluated using enzyme-linked immunosorbent assay and glucose oxidase technique, respectively. Insulin resistance index (HOMA-IR) was measured as well.
Results: The mean±SD plasma adiponectin concentration of the CRC patients (7.98±0.64 ng/ml) was not significantly higher, compared to that in the control group (8.05±1.14 ng/mL). The mean±SD of HOMA-IR and plasma glucose levels (1.81±0.61 and 7.64±1.34 mm/L, respectively) of the CRC group were significantly higher (P<0.05), compared to the control group (1.37±0.3 and 119±1.1 mg/dL, respectively); however, plasma insulin wasn’t significantly different in the two study groups. Following the stratification of CRC patients according to the tumor site, a significantly lower level of adiponectin (7.36 ±1.1 ng/ml) (P<0.05) and a significantly higher level of HOMA-IR (2.08±0.44) were observed in patients with colon cancer (P<0.005), compared to the controls. Regression among the plasma adiponectin and the plasma insulin and HOMA was negative in the control and CRC groups.
Conclusion: Insulin resistance has an important role in the development of CRC, especially in genesis colon cancer, regardless of the change that it causes in plasma levels of adiponectin
The ghrelin system contains several components (e.g., ghrelin with growing number of alternative peptides, growth hormone secretagogue receptors (GHS-Rs), and ghrelin-O-acyl-transferase (GOAT) and participates in regulation of a number of key processes of gastrointestinal (GI) tract cancer progression, including cell proliferation, migration, invasion, apoptosis, inflammation, and angiogenesis. However, its exact role in promoting or inhibiting cancer progression is still unclear. Colorectal cancer (CRC) is one of the most common human malignancies worldwide. Molecular studies suggest an autocrine/paracrine mechanism for the secretion of ghrelin in colorectal carcinogenesis and its contribution to its initial stages. However, the signalling pathways of CRC development involving the ghrelin system are poorly understood. Potential mechanisms of colon carcinogenesis involving components of the ghrelin system were previously described in an animal model and in in vitro studies. However, the diagnostic–prognostic role of serum ghrelin concentrations, tissue expression, or genetic changes of this system in various stages of CRC progression remains an open case. Thus, the aim of this study is to discuss the role of the ghrelin system in colon carcinogenesis, diagnostics and CRC prognostics, as well as the results of studies on the use of ghrelin and its analogues in the therapy of CRC-related syndromes (e.g., cachexia and sarcopenia).
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