Cucurbitacin enhances insulin sensitivity via GLUT4 translocation.

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Journal name: World Journal of Pharmaceutical Research
Original article title: Cucurbitacin augments insulin sensitivity and glucose uptake through translocation and activation of glut4 in pi3k/akt signaling pathway
The WJPR includes peer-reviewed publications such as scientific research papers, reports, review articles, company news, thesis reports and case studies in areas of Biology, Pharmaceutical industries and Chemical technology while incorporating ancient fields of knowledge such combining Ayurveda with scientific data.
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Original source:

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Author:

Gani Sharmila Banu


World Journal of Pharmaceutical Research:

(An ISO 9001:2015 Certified International Journal)

Full text available for: Cucurbitacin augments insulin sensitivity and glucose uptake through translocation and activation of glut4 in pi3k/akt signaling pathway

Source type: An International Peer Reviewed Journal for Pharmaceutical and Medical and Scientific Research

Doi: 10.20959/wjpr20178-8924


Download the PDF file of the original publication


Summary of article contents:

Introduction

Diabetes mellitus is a global metabolic disorder characterized by persistent hyperglycemia due to either impaired insulin production or insulin resistance. The prevalence of diabetes is escalating, with projections estimating that the number of individuals affected will nearly double by 2035. In the quest for effective treatment options, natural compounds, particularly from the Cucurbitaceae family, have garnered attention for their potential antidiabetic effects. Cucurbitacin, a triterpenoid derived from various plants, has shown promise in enhancing insulin sensitivity and glucose uptake, making it a subject worthy of investigation in diabetic animal models.

Enhanced Glucose Uptake Through PI3K/Akt Pathway

One of the primary focuses of the study was to explore how cucurbitacin improves glucose uptake in skeletal muscle. Insulin is pivotal in promoting glucose transport into cells, and its action is mediated through a signaling cascade involving phosphoinositide 3-kinase (PI3K) and the serine/threonine kinase Akt. The administration of cucurbitacin significantly increased the phosphorylation of insulin signaling proteins, including insulin receptor (IR), insulin receptor substrates (IRS-1 and IRS-2), PI3K, and Akt. This enhancement facilitated GLUT4 translocation to the plasma membrane, thereby increasing glucose uptake. These findings indicate that cucurbitacin plays a substantial role in modulating insulin signaling, which is crucial for maintaining glucose homeostasis.

Antioxidant Effects of Cucurbitacin

Diabetes is often associated with oxidative stress, leading to increased lipid peroxidation and decreased antioxidant defenses. In this study, the administration of cucurbitacin mitigated oxidative stress by significantly reducing levels of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides in diabetic rats. Additionally, it improved the activities of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), along with non-enzymatic antioxidants like vitamins C and E. These results suggest that cucurbitacin possesses antioxidant properties that can ameliorate oxidative stress, which is particularly severe in diabetic conditions.

Role of PPAR-γ in Insulin Sensitivity

The study also examined the effect of cucurbitacin on peroxisome proliferator-activated receptor gamma (PPAR-γ), a key regulator of glucose and lipid metabolism. PPAR-γ expression is often downregulated in insulin-resistant states. The results demonstrated that treatment with cucurbitacin led to an increase in PPAR-γ expression in the skeletal muscle of diabetic rats. This implies that cucurbitacin not only enhances insulin signaling but may also contribute to better metabolic regulation through the modulation of PPAR-γ, which could be vital in managing diabetes and its complications.

Conclusion

In summary, the findings from this study indicate that cucurbitacin possesses significant antidiabetic effects by enhancing glucose uptake and improving insulin sensitivity through the PI3K/Akt signaling pathway. Additionally, its antioxidant properties reduce oxidative stress, further aiding metabolic health. The upregulation of PPAR-γ suggests a multifaceted approach by which cucurbitacin could prevent the progression of diabetes and its associated complications. These results provide a compelling rationale for further investigation into cucurbitacin as a potential therapeutic agent in managing diabetes and its metabolic disorders.

FAQ section (important questions/answers):

What is the role of cucurbitacin in diabetes treatment?

Cucurbitacin improves glucose uptake in skeletal muscles, enhancing insulin sensitivity and activating the PI3K/Akt signaling pathway, which helps maintain blood glucose homeostasis.

How does cucurbitacin affect plasma glucose levels in diabetic rats?

Administration of cucurbitacin significantly reduces elevated plasma glucose levels in STZ-induced diabetic rats, bringing them closer to normal rates.

What were the experimental conditions for the study on cucurbitacin?

The study involved male Wistar albino rats induced with diabetes using streptozotocin and treated with cucurbitacin to assess its effects on glucose metabolism.

Which antioxidants were measured in the study with cucurbitacin?

The study measured enzymatic antioxidants like SOD, CAT, GPx, and non-enzymatic antioxidants such as vitamins C and E, showing improvements after treatment.

What does the insulin signaling analysis reveal about cucurbitacin?

Cucurbitacin administration increased the expression of insulin signaling proteins, including IR, IRS-1, Akt, and GLUT4, indicating enhanced insulin sensitivity.

What are the overall findings regarding cucurbitacin's effects?

Cucurbitacin exhibits strong antioxidant effects, improves insulin secretion, and enhances glucose uptake, suggesting potential for diabetes prevention and treatment.

Glossary definitions and references:

Scientific and Ayurvedic Glossary list for “Cucurbitacin enhances insulin sensitivity via GLUT4 translocation.”. This list explains important keywords that occur in this article and links it to the glossary for a better understanding of that concept in the context of Ayurveda and other topics.

1) Animal:
In the context of this study, 'animal' refers specifically to the male Wistar albino rats used for experimentation. Animal models are essential in biomedical research as they allow scientists to study disease processes and potential treatments in a living organism, providing insights that cannot be obtained from in vitro studies alone.

2) Study (Studying):
A 'study' in this context pertains to the scientific investigation conducted to analyze the effects of cucurbitacin on glucose uptake and insulin signaling pathways in diabetic rats. Studies are systematic investigations aimed at discovering or testing hypotheses and results help establish a foundation for future research and therapeutic interventions.

3) Post:
'Post' is used here in the context of the experimental timeline when referencing the actions or measurements taken after a specific event, like administering treatment. In scientific literature, 'post' often indicates the period after an intervention when researchers monitor effects, contributing to the understanding of temporal dynamics in biological responses.

4) Blood:
'Blood' refers to the bodily fluid containing red cells, white cells, platelets, and plasma, which is crucial in transporting nutrients, gases, hormones, and waste products. In this study, blood analysis helps in understanding metabolic changes, insulin levels, and glucose concentration in response to treatments administered to the diabetic rats.

5) Species:
'Species' identifies the different categories of living organisms, here referring to the specific type of rats used in the research. Understanding species allows researchers to generalize findings or compare data across different organisms, providing insights into biological mechanisms that may be similar in humans, influencing drug development and therapies.

6) India:
'India' is the geographical and cultural context in which this research is conducted. The mention of India emphasizes the relevance of local dietary practices, medicinal plants like cucurbitacin, and metabolic diseases in the region, making the research findings particularly pertinent for public health initiatives and diabetes management strategies in India.

7) Family:
'Family' in this context refers to the taxonomic classification of organisms, specifically the Cucurbitaceae family to which cucurbitacin belongs. Understanding the family of a substance helps in assessing its biological properties, effectiveness in various medicinal applications, and potential benefits or toxicities when consumed as part of a traditional diet.

8) Cancer:
'Cancer' is referenced to describe the potential of cucurbitacin in exhibiting cytotoxic effects against various cancer cell lines. The study illuminates how certain natural compounds can have therapeutic effects beyond glucose regulation, highlighting the versatility of cucurbitacin as a candidate for cancer treatment alongside diabetes management.

9) Diet:
'Diet' refers to the habitual food and drink choices made by individuals, particularly in the context of a traditional Indian diet that includes various vegetables with potential health benefits. This emphasizes the importance of dietary habits in managing metabolic disorders like diabetes, showcasing how food compounds play a restorative role.

10) Tamilnadu (Tamil-nadu):
'Tamilnadu' is the Indian state where this research is conducted, emphasizing the local context of the study. This regional focus can affect both the selection of plant-based compounds studied due to accessibility and contributes to cultural practices regarding diet and health, providing a backdrop for understanding local health issues.

11) Relative:
'Relative' in this text describes comparisons made in the study between different experimental groups or measures. This comparative analysis helps in demonstrating the efficacy of treatments and employing statistical methods to derive conclusions about the effectiveness of cucurbitacin and other substances in managing diabetes.

12) Zoology:
'Zoology' is the aspect of biology that studies animals and their physiological processes. As the research is conducted in the Department of Zoology, it underscores the biological focus of the experiments and how animal models contribute essential insights into human health and disease management, specifically in metabolic disorders.

13) Water:
'Water' in the experimental context refers to the fluid essential for life that ensures biological functions and supports metabolic processes. It is vital for maintaining hydration in animal subjects during the study and serves as a solvent for various treatments and compounds, highlighting the significance of proper fluid balance in research.

14) Gani:
'Gani' refers to Dr. Gani Sharmila Banu, the corresponding author of the study. The acknowledgment of authorship is crucial in scientific literature, providing a point of contact for inquiries and establishing credibility, as researchers rely on the academic qualifications and contributions of authors to validate findings.

15) Human body:
'Human body' denotes the target of relevance for the research findings, linking animal study results to human physiology. Insights gained from animal models can inform understanding of insulin signaling and glucose metabolism in humans, further bridging the gap between preclinical research and potential clinical applications.

16) Trichosanthes dioica:
'Trichosanthes dioica' is a specific plant species known for its edible parts and medicinal properties, including hypoglycemic effects. The study emphasizes the significance of this plant as a source of cucurbitacin and its therapeutic potential for managing diabetes, illustrating the importance of traditional knowledge in contemporary research.

17) Discussion:
'Discussion' refers to the section of the study where the results are interpreted and contextualized within the existing body of scientific knowledge. This critical analysis allows researchers to extrapolate implications from their findings, address limitations, relate to other studies, and suggest directions for future research, enhancing overall scientific understanding.

18) Developing:
'Developing' pertains to countries or regions, such as India, where the study is pertinent due to rising health challenges like diabetes. This term underscores the urgent need for effective interventions and research tailored to the health contexts of developing nations facing rapid socioeconomic changes and increasing prevalence of lifestyle-related diseases.

19) Substance:
'Substance' refers to a particular chemical or compound, in this case, cucurbitacin. Understanding the properties of a substance is crucial for exploring its potential health benefits, mechanisms of action, and how it can be utilized in therapeutic approaches to treat diseases such as diabetes and complications arising from it.

20) Bitter:
'Bitter' describes the taste associated with cucurbitacins, which are known for their distinctively bitter flavor profile. This characteristic is significant as it influences dietary acceptance and use, impacting how plants containing cucurbitacin are integrated into traditional medicines and cuisines, thereby affecting therapeutic applications.

21) Santa (Shanta, Samta, Shamta):
'Santa' refers to Santa Cruz Biotechnology, the supplier of antibodies utilized in the experiments. Acknowledging suppliers adds a layer of credibility and reliability to research and highlights the importance of using quality reagents, which can affect the validity and reproducibility of experimental results.

22) Simha:
'Sinha' denotes a method referenced in the biochemical analysis for estimating catalase levels. The mention of specific methods enriches the research by providing a framework from which new methodologies can be developed or previously established knowledge can be expanded, ensuring scientific rigor in data collection and analysis.

23) House:
'House' here contextualizes the animal facilities where the experiments were conducted, highlighting the significance of ethical considerations and proper care within laboratory settings. Maintaining appropriate conditions ensures the welfare of study animals and adherence to institutional guidelines, which is paramount in responsible scientific research.

24) Java:
'Java' refers to the public domain software used for image processing in the study. Utilizing open-source tools facilitates data analysis and enhances the transparency of research methodologies, allowing for reproducibility of results which is essential for validating experimental outcomes and fostering collaborative scientific efforts.

25) Meat:
'Meat' is referenced concerning the diet and culinary practices involving the consumption of animal flesh. This mention can suggest the role of different food groups in a balanced diet and the implications of dietary habits on health, especially in metabolic disorders like diabetes where carbohydrate management is crucial.

26) Line:
'Line' in scientific terms often indicates a lineage or category, such as referring to specific animal strains or cell lines. Understanding the lineage allows researchers to ascertain genetic factors that may influence response to treatments and contributes to the overall understanding of disease mechanisms across different biological contexts.

27) Drug:
'Drug' signifies any active compound used for therapeutic purposes, such as glibenclamide noted in the study. Identifying drugs helps establish benchmarks against which the efficacy of new compounds, like cucurbitacin, can be compared, enriching the pharmaceutical landscape and contributing to better treatment protocols.

28) Shash (Sas, Sash, Sad, Shas, Shad):
'Shad' appears in the context of animal maintenance protocols. Its use underscores the importance of establishing and adhering to standards for the housing and care of experimental animals, which is essential for producing reliable data and ensuring the well-being of subjects in scientific trials.

29) Male:
'Male' specifically denotes the gender of the Wistar albino rats used in this research. The gender of animal subjects in studies can influence biological responses to treatments, making it imperative to control for sexual dimorphism during experiments, ensuring that findings can be accurately interpreted and applied broadly.

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