Introduction: What they say
A study from the Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, Florida 33458, USA shows that “Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists.” This research paper was published, in the 29 March 2012 issue of the journal “Nature” [One of the best research journals in Science with an I.F of 43 plus], by Prof.Burris TP, Solt LA and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Mechanistic insights into how Liraglutide aids in control of body weight, energy homeostasis and TIIDM: Liraglutide (brand name: Victoza, Saxenda and others), a drug used in the treatment of type II diabetes, increases REV-ERB and its down stream target genes, inhibits lipid accumulation, improves dyslipidemia and insulin sensitivity, increases energy utilization, promotes weight loss and protects from diet-induced obesity and TIIDM, via up regulation of its target gene
From significance of the study to public health relevance:
Given that: (1) more than half a billion adults are obese worldwide ; (2) obesity is more prevalent in western countries than in asian countries; (3) obesity results in deregulated blood pressure, cholesterol, triglycerides and insulin sensitivity; and the risks of coronary heart disease, ischemic stroke and TII diabetes mellitus(TIIDM) increase ; (4) more than 422 million people worldwide are affected by Diabetes mellitus (DM); (5) Diabetes is going to be one of the top 10 causes of death by 2030; (6) the life-long painful injection/drug treatment is required to treat DM; and (7) the global economic cost spent for diabetes treatment in 2014 was little more than 600 billion US dollars, there is an urgent need to find: (i) a way to induce regeneration of adult ß-cells that were lost in DM; (ii) a cheaper alternative to the existing expensive weight-loss drugs; (iii) a side-effect-free natural product-based drug; and (iv) a way to cure, not just treat, obesity-associated diseases, including diabetes.
What is known?
Prof.Burris’s research team has recently shown that administration of REV-ERB ligands:(1) regulates circadian behaviour and the circadian pattern of core clock gene;(2) alters the circadian pattern of expression of metabolic genes in liver, skeletal muscle and adipose tissue; (3) increases energy expenditure; (4) inhibits lipid accumulation; (4) decreases obesity; (5) improves dyslipidemia; and (6) reduces hyperglycaemia, suggesting that increasing the expression of REV-ERB may promote weight loss, augment insulin sensitivity, improve dyslipidemia and alleviate Obesity-associated TIIDM.
From Research findings to Therapeutic opportunity:
I had suggested earlier (on 14/November/2017 at 5.14 am and in others) that how Victoza/Saxenda/Liraglutide may improve insulin sensitivity and protect against obesity and diabetes (https://genomediscovery.org/2017/11/molecular-therapy-for-tiidm-and-obesity-associated-metabolic-deficits-victozasaxenda-a-drug-used-in-the-treatment-of-tiidm-and-obesity-increases-lipocalin-2-lcn2-expression-activates/).
Evidently, a very recent study from the Department of Pediatrics, Yale University, New Haven, CT; Pediatric Endocrinology, Angeles Hospital of Puebla, Puebla City, Mexico; Novo Nordisk, Søborg, Denmark; the Diabetes and Endocrinology Unit, Department of Paediatrics, Cairo University, Cairo; Novo Nordisk, Plainsboro, NJ; Institute of Cancer and Genomic Sciences, University of Birmingham,and Birmingham Women’s and Children’s Hospital, Birmingham, United Kingdom and others shows that “Liraglutide in Children and Adolescents with Type 2 Diabetes.” This study was published, in the 28 April 2019 issue of of the prestigious journal N Engl J Med. (NEJM) (Impact factor: 79.258+), by Prof. Timothy Barrett, Tamborlane and others. This study suggests that Liraglutide, in conjunction with Metformin, is efficacious in improving glycemic control in children and adolescents with type II diabetes. However, the precise mechanism of action of this drug remains largely unclear.
This study substantiates their claim by providing a detailed mechanistic insights into how Liraglutide may aid in attenuating insulin resistance and in the treatment of weight loss and obesity-associated TIIDM.
Liraglutide, by increasing the expression of its target gene, it may increase the expression of REV-ERB (Fig.1). Thereby, it may: (1) normalize circadian pattern of metabolic genes; (2) augment energy expenditure; (3) inhibit lipid accumulation; (4) promote weight loss; (5) ameliorate dyslipidemia; and (6) inhibit hyperglycemia (Fig.1).
Thus, pharmacological formulations encompassing “Liraglutide or its analogues , either alone or in combination with other drugs” may be used:(i) as a weight-loss medication; (ii) to treat Obesity-associated TIIDM; (iii) to treat sleep disorders (Fig.2).
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
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Undisclosed mechanistic information: How does Liraglutide increase the expression of REV-ERB?
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Citation: Boominathan, L., Mechanistic insights into how Liraglutide aids in control of body weight, energy homeostasis and TIIDM: Liraglutide (brand name: Victoza, Saxenda and others), a drug used in the treatment of type II diabetes, increases REV-ERB and its down stream target genes, inhibits lipid accumulation, improves dyslipidemia and insulin sensitivity, increases energy utilization, promotes weight loss and protects from diet-induced obesity and TIIDM, via up regulation of its target gene, 4/May/2019, 12.27 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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