Mechanistic insights into how Liraglutide may aid in the treatment of Diabetes: Liraglutide (brand name: Victoza, Saxenda, others), an acylated glucagon-like peptide-1 (GLP-1) agonist used in the treatment of Type II diabetes, increases GLP1R and Caveolin-1 (CAV-1) expression, promotes glucose-induced insulin secretion, improves insulin sensitivity, increases energy utilization, promotes weight loss and protects from diet-induced obesity and TIIDM, via up-regulation of its target gene, 5/May/2018, 7.09 am

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Introduction: What they say

A study from the Comprehensive Diabetes Center and Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, the University of Alabama at Birmingham, Birmingham, AL shows that “miR-204 Controls Glucagon-Like Peptide 1 Receptor Expression and Agonist Function.” This research paper was published, in the 3 November 2017 issue of the journal “Diabetes” [One of the best research journals in diabetic research with an I.F of 10 plus], by Prof. Shalev A, Jo S 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 may aid in the treatment of Diabetes: Liraglutide (brand name: Victoza, Saxenda, others), an acylated glucagon-like peptide-1 (GLP-1) agonist used in the treatment of Type II diabetes, increases GLP1R and Caveolin-1 (CAV-1) expression, promotes glucose-induced insulin secretion, improves 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 422 million people worldwide are affected by Diabetes mellitus (DM); (2) Diabetes is going to be one of the top 10 causes of death by 2030; (3) the life-long painful injection/drug treatment is required to treat DM; (4) 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, diabetes.


What is known?

Prof. Shalev A’s research team has recently shown that:(1) MiRNA-204, the highly expressed miRNA in ß-cells, inhibits GLP1R expression; (2) deletion of miR-204: (a) increases cAMP production; (b) increases insulin secretion; (c) augments response to GLP1R activators or agonists; and (d) protects against diabetes; (3) deletion of thioredoxin-interacting protein, the upstream regulator of miR-204, (a) increases GLP1R expression; (b) ameliorates glucose intolerance; (c) improves cAMP production; (d) increases insulin secretion; and (e) protects against diabetes, suggesting that decreasing the expression of MiR-204 or its upstream regulator thioredoxin-interacting protein may promote insulin sensitivity, and alleviate TIIDM.


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 GLP1R and Caveolin-1 (CAV-1). Thereby, it may: (1) increase pancreatic beta-cell proliferation; (2) increase the expression of genes that promote insulin sensitivity and insulin secretion; (3) promote weight loss; (4) augment energy expenditure; (5) decrease metabolic stress; and (6) promote energy homeostasis (Fig.1). Thus,  pharmacological formulations encompassing “Liraglutide or its analogs, either alone or in combination with other drugs,” may be used to treat TIIDM (Figure 2).

Figure 1. Mechanistic insights into how Liraglutide functions as an antidiabetic agent. Liraglutide, by up-regulating its target genes, it may: a) increase cAMP levels; b) increase insulin sensitivity; c) increase secretion; and d) attenuate hyperglycemia

Figure 2. Liraglutide functions as an anti-diabetic agent through induction of CAV1 and GLP-IR.


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Undisclosed information: How does Liraglutide increase the expression of GLP1R and CAV-1?

Amount: $500#

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References:

Web: http://genomediscovery.org  or http://newbioideas.com

Citation: Boominathan, L., Mechanistic insights into how Liraglutide may aid in the treatment of Diabetes: Liraglutide (brand name: Victoza, Saxenda, others), an acylated glucagon-like peptide-1 (GLP-1) agonist used in the treatment of Type II diabetes, increases GLP1R and Caveolin-1 (CAV-1) expression, promotes glucose-induced insulin secretion, improves insulin sensitivity, increases energy utilization, promotes weight loss and protects from diet-induced obesity and TIIDM, via up-regulation of its target gene, 5/May/2018, 7.09 am, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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