Novel targets for new insulin sensitizers and glucose-lowering agents.

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Journal name: World Journal of Pharmaceutical Research
Original article title: Identification of novel targets of new insulin sensitizers- studies of related mechanism with other glucose-lowering agents
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Original source:

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Author:

Mohammed H F Shalayel, Moawia A Elbadri, Ihab Hamed Nourein, Ietimad AM Ayed, Mohammed Ayed Huneif


World Journal of Pharmaceutical Research:

(An ISO 9001:2015 Certified International Journal)

Full text available for: Identification of novel targets of new insulin sensitizers- studies of related mechanism with other glucose-lowering agents

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


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Summary of article contents:

Introduction

Diabetes is a significant global health issue, affecting over 5% of the world's population. Projections estimate that the prevalence of diabetes could rise dramatically, with figures expected to increase from 150 million in 2000 to 300 million by 2025. As the disease evolves, managing hyperglycemia, particularly in type 2 diabetes patients who may require insulin, becomes increasingly complex. This paper aims to explore novel targets for insulin sensitizers, including Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, G-protein-coupled receptors (GPCRs), and thiazolidinediones, emphasizing personalized treatment strategies to address the multifaceted nature of diabetes.

Exploring SGLT-2 Inhibitors

SGLT-2 inhibitors represent a new class of glucose-lowering agents that function by inhibiting glucose reabsorption in the kidneys, thus increasing urinary glucose excretion. These agents not only improve glycemic control but also demonstrate potential cardiovascular benefits by lowering blood pressure and promoting weight loss. Common SGLT-2 inhibitors such as empagliflozin, canagliflozin, and dapagliflozin are examined for their effectiveness in reducing HbA1c levels and aiding in the management of type 2 diabetes. However, side effects, including genital infections and volume depletion, warrant careful consideration when prescribing these medications.

G-Protein-Coupled Receptors as Drug Targets

G-protein-coupled receptors (GPCRs) present novel drug targets in the treatment of diabetes. These receptors respond to various extracellular stimuli and are implicated in several physiological processes. Free fatty acids acting as ligands for specific GPCRs, such as GPR120 and GPR119, have been found to influence insulin secretion and glucose metabolism. The interaction of fatty acids with these receptors can contribute to both insulin resistance and secretion. Continued research on GPCRs holds promise for developing therapies that improve diabetic conditions by either enhancing insulin sensitivity or promoting β-cell function.

Advancements in Thiazolidinediones

Thiazolidinediones (TZDs) are another class of agents in diabetes management, primarily acting as PPAR-γ agonists to enhance insulin sensitivity. While exerting beneficial metabolic effects, TZDs have been associated with several side effects, including significant weight gain and fluid retention. Recent investigations into PPAR-γ-sparing TZDs aim to separate the therapeutic effects from adverse outcomes, demonstrating that insulin-sensitizing effects can be achieved without activating PPAR-γ. Studies regarding novel compounds suggest that targeting mitochondrial pathways may open new doors for developing safer and effective TZDs in clinical practice.

Conclusion

As diabetes management continues to evolve, identifying novel therapeutic targets and personalized approaches is essential for improving patient outcomes. Agents such as SGLT-2 inhibitors and advances in GPCR research, alongside improved understanding of thiazolidinediones, represent significant progress in the treatment of type 2 diabetes. Ultimately, incorporating these innovations will enhance the individualization of diabetes therapies, paving the way for more effective and sustainable management strategies. Ongoing research remains crucial for understanding the intricate relationships between these drugs and their metabolic effects, ensuring optimal care for individuals diagnosed with diabetes.

FAQ section (important questions/answers):

What are the main aims of this research on insulin sensitizers?

The research aims to identify novel targets for insulin sensitizers, focusing on mechanisms such as SGLT-2 inhibitors, GPCRs, thiazolidinediones, and stem cell therapy to improve therapeutic interventions.

Why is diabetes considered a major global health problem?

Diabetes affects over 5% of the world's population, with forecasts predicting substantial increases in prevalence. Effective management and new treatments are needed to address the complexities of diabetes care.

What mechanisms do current diabetes treatments target?

Current treatments target insulin deficiency, insulin resistance, and increased hepatic glucose output, aiming to correct physiological abnormalities associated with type 2 diabetes.

What role do SGLT-2 inhibitors play in diabetes management?

SGLT-2 inhibitors help lower blood glucose levels by increasing renal glucose excretion, promoting weight loss, and potentially reducing cardiovascular risk in patients with type 2 diabetes.

How do GPCRs relate to diabetes treatment?

GPCRs are important drug targets that respond to extracellular stimuli. They modulate insulin secretion and other physiological processes, making them significant in developing new diabetes medications.

What are the potential benefits of stem cell therapy for diabetes?

Stem cell therapy could offer beta cell replacement, improving insulin secretion in Type 1 diabetes, but challenges include immunosuppression and limited donor availability for islet transplantation.

Glossary definitions and references:

Scientific and Ayurvedic Glossary list for “Novel targets for new insulin sensitizers and glucose-lowering agents.”. 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) Drug:
A drug is a chemical substance used to treat, prevent, or diagnose a disease or medical condition. In diabetes treatment, various classes of drugs are employed to manage blood sugar levels, including insulin sensitizers, SGLT2 inhibitors, and thiazolidinediones, each targeting specific metabolic pathways to improve patient outcomes.

2) Blood:
Blood plays a crucial role in transporting oxygen, nutrients, hormones, and waste products throughout the body. In the context of diabetes, blood glucose levels are a key focus for management, as maintaining optimal blood sugar levels is essential for preventing complications associated with the disease, such as cardiovascular issues and neuropathy.

3) Disease:
A disease is a pathological condition of a bodily part, an organism, or system resulting from various causes such as infection, genetic defect, or environmental stress. Diabetes mellitus is a chronic disease characterized by insulin resistance and deficiency, necessitating a multifaceted treatment approach to manage symptoms and complications.

4) Medicine:
Medicine refers to the science and practice of diagnosing, treating, and preventing diseases. In diabetes care, medicine encompasses pharmacological therapies, lifestyle modifications, and patient education strategies aimed at achieving glycemic control and minimizing long-term complications associated with the condition, improving the overall quality of life for patients.

5) Nausea:
Nausea is an unpleasant sensation frequently preceding vomiting, often associated with gastrointestinal issues or the side effects of medication. In diabetes treatment, certain drugs, particularly GLP-1 receptor agonists, can cause nausea, impacting patient adherence to therapy. Managing side effects like nausea is vital for successful treatment outcomes.

6) Study (Studying):
A study is a formal investigation into a particular subject to acquire new knowledge or validate existing theories. The article discusses numerous studies assessing the efficacy and safety of various glucose-lowering agents in type 2 diabetes, providing insights into their mechanisms of action and therapeutic potential for personalized medicine.

7) Beta:
Beta refers to beta cells located in the pancreas, which are responsible for producing insulin. In diabetes, dysfunction or destruction of these cells is a fundamental issue leading to the condition. Targeting beta-cell health is crucial for developing effective therapies aimed at sustaining insulin production and regulating blood glucose levels.

8) Life:
Life refers to the existence of individuals or organisms and encompasses various aspects such as health and well-being. In the context of diabetes, the quality of life can be significantly affected by the disease, making it essential to implement effective treatments that help patients manage their condition and live fulfilling lives.

9) Pharmacology:
Pharmacology is the branch of medicine concerned with the study of drug action and how drugs interact with biological systems. Understanding pharmacology is essential for developing new diabetes medications that target specific pathways in glucose metabolism, improving treatment efficacy while minimizing adverse effects for better patient management.

10) Vomiting:
Vomiting is the involuntary expulsion of stomach contents through the mouth, often a response to nausea or irritation. Some diabetes medications, particularly those that affect gastrointestinal motility, may lead to vomiting as a side effect, necessitating careful monitoring and adjustments in treatment to enhance patient compliance and outcomes.

11) Training:
Training involves educating healthcare professionals and patients on diabetes management strategies, including insulin administration, medication adherence, and self-monitoring of blood glucose levels. Proper training is crucial for ensuring that patients can effectively manage their condition, recognize symptoms, and respond appropriately to changes in their health status.

12) Animal:
Animal studies play a significant role in biomedical research, particularly in understanding disease mechanisms and testing new therapies. Research involving animal models helps elucidate the pathophysiology of diabetes, test pharmacological agents, and evaluate potential side effects before advancing to human clinical trials, ensuring safer drug development.

13) Bile:
Bile is a digestive fluid produced by the liver that aids in the digestion of fats. Research has shown that bile acids can influence glucose metabolism and insulin sensitivity, leading to interest in developing medications that target bile acid signaling pathways as a novel approach to treat diabetes and related metabolic disorders.

14) Channel:
A channel refers to a pathway through which substances like ions or molecules travel across cell membranes. In diabetes, ion channels play critical roles in insulin secretion and action. Understanding these channels is essential for developing new therapeutics that enhance or modulate insulin action, improving glycemic control in patients.

15) Science (Scientific):
Science is a systematic enterprise that builds and organizes knowledge in the form of testable explanations and predictions about the universe. The development of new diabetes treatments relies heavily on scientific research, informing evidence-based practices and guiding clinicians in choosing appropriate therapies to manage the disease effectively.

16) Cancer:
Cancer is a disease characterized by the uncontrolled growth of abnormal cells. Certain diabetes medications have been scrutinized for their potential links to increased cancer risk. This necessitates ongoing research to ensure that diabetes treatments not only control blood glucose but also do not exacerbate the risk of developing malignancies.

17) Edema (Oedema):
Edema is the swelling caused by excess fluid trapped in the body’s tissues. Some diabetes medications, especially thiazolidinediones, are associated with fluid retention leading to edema. Understanding this side effect is crucial for clinicians to manage patient treatment plans and mitigate risks of complications related to fluid buildup.

18) Table:
A table provides a structured format for presenting data in a clear and concise manner, essential for comparing the properties and effects of various glucose-lowering agents. Tables in scientific literature facilitate quick reference and understanding of complex information, aiding clinicians in making informed treatment decisions for diabetes management.

19) Pharmacological:
Pharmacological pertains to the study of drugs and their effects on biological systems. The pharmacological properties of diabetes medications determine their effectiveness in managing hyperglycemia and influencing metabolic pathways. Understanding these properties aids researchers and clinicians in selecting the most suitable therapies for individual patient needs in diabetes care.

20) Accumulation (Accumulating, Accumulate):
Accumulation refers to the gradual gathering or increased concentration of a substance. In diabetes management, the accumulation of glucose in the blood due to insulin resistance signifies poor glycemic control. Addressing this accumulation through pharmacological intervention and lifestyle modifications is crucial for effective diabetes management and health improvement.

21) Inflammation:
Inflammation is the body's immune response to harmful stimuli, often leading to tissue damage. In diabetes, chronic low-grade inflammation contributes to insulin resistance and metabolic dysregulation. Understanding the inflammatory pathways is critical for developing therapeutics that target these processes, potentially improving insulin sensitivity and overall disease management.

22) Observation:
Observation involves monitoring and assessing a patient's condition or the effects of treatment over time. In clinical diabetes research, systematic observation helps identify the efficacy and safety of therapies, contributing to evidence-based practices that enhance patient outcomes and refine therapeutic strategies for managing type 2 diabetes.

23) Education:
Education encompasses the process of imparting knowledge and skills. In diabetes management, patient education is vital for self-care, medication adherence, and lifestyle modifications. Empowering patients with knowledge improves their ability to manage their condition effectively, enhancing their quality of life and reducing the risk of complications associated with the disease.

24) Toxicity:
Toxicity refers to the degree to which a substance can harm humans or animals. Understanding the toxicity profiles of diabetes medications is essential for ensuring patient safety, guiding clinicians in selecting appropriate treatments, and minimizing adverse effects that could compromise the overall management of the disease.

25) Mutation:
Mutation is a change in the DNA sequence that can lead to altered function of genes and proteins. Genetic mutations may influence an individual's susceptibility to diabetes or response to treatment. Researching these mutations helps personalize therapy approaches, leading to more effective management strategies based on genetic profiles.

26) Activity:
Activity relates to the biochemical or physiological processes facilitated by drugs or hormones. In diabetes, assessing the activity of insulin and other glucose-lowering agents is crucial for understanding their effectiveness in managing blood sugar levels and guiding treatment plans to achieve optimal glycemic control in patients.

27) Relative:
Relative refers to the degree of association or comparison between two or more entities. In diabetes research, examining relative risks associated with specific medications or treatment approaches helps inform clinicians about potential outcomes and aids in making informed decisions about the safest and most effective therapies for patients.

28) Meeting:
Meeting pertains to a gathering of individuals to discuss and exchange information. In medical research, formal meetings help disseminate study findings, develop collaborative efforts, and advance knowledge in the field of diabetes management, ultimately contributing to improved treatment guidelines and patient care practices.

29) Surface:
Surface refers to the outer or top layer of an object. In pharmacology, drug interactions with cell surface receptors are crucial for understanding how medications exert their effects. Surface receptors often mediate the action of insulin and other diabetes drugs, influencing their therapeutic outcomes and safety profiles.

30) Family:
Family refers to a group of related individuals. In diabetes research, familial patterns can provide insights into genetic predispositions to the disease. Understanding these familial links aids in early identification, intervention strategies, and the development of tailored treatments for individuals with a family history of diabetes.

31) Medium:
Medium can refer to a substance or environment in which biological reactions take place. In laboratory settings, culture media support the growth of cellular specimens to test new diabetes treatments. Understanding how different media affect cellular responses is vital for advancing research in medication development and testing.

32) Death:
Death signifies the permanent cessation of all biological functions that sustain a living organism. In diabetes, mortality risk can be significantly influenced by poor glycemic control and the presence of complications. Understanding these risks helps clinicians focus on treatment strategies that enhance longevity and quality of life for patients.

33) Cutan:
Sudan, a country in northeastern Africa, is referenced in the study as a location for research institutions involved in diabetes studies. Including diverse geographic populations in research enhances the understanding of diabetes prevalence, risk factors, and treatment responses across different communities and informs tailored intervention programs.

34) Ovid:
Ovid is a digital platform providing access to a vast array of scientific literature and databases. Utilizing Ovid in diabetes research enables investigators to access up-to-date studies, clinical trials, and systematic reviews, facilitating informed decision-making and contributing to evidence-based practices in diabetes treatment and management.

35) Food:
Food refers to substances consumed for nutrition and energy. In diabetes management, dietary choices significantly impact blood glucose levels. Understanding the influence of different foods on glycemic control is essential for developing dietary guidelines that support effective diabetes management and improve patients' quality of life.

36) Diet:
Diet refers to the food and drink habits of individuals. In diabetes management, adopting a balanced and controlled diet is crucial for maintaining blood sugar levels. Education on dietary choices empowers individuals to make informed decisions that can positively impact their health and glycemic control, reducing complications associated with diabetes.

37) Pose:
Pose indicates a challenge or an approach to addressing a situation. In diabetes management, physicians often pose questions regarding individual treatment plans to tailor therapies based on patient-specific needs. Understanding these unique factors allows for the development of personalized strategies that enhance treatment adherence and outcomes.

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